Exam 1 Flashcards
Intro to the nervous system, Nerve electrophysiology, ANS, Muscle physiology, CV physiology, Electrical activity of the heart
1
Q
CNS is made up of:
A
Brain and spinal cord
2
Q
PNS is made up of:
A
Cranial nerves and spinal nerves ( and their branches)
3
Q
PNS is divided into:
A
Sensory (afferent) division and motor (efferent) division
4
Q
Sensory division of PNS divisions
A
Somatic Sensory: Carries general sensory signals from muscles, bones, joints and the skin, as well as special sensory signals to the CNS
Visceral Sensory: Carries signals from organs to the CNS
AFFERENT!!!!!
5
Q
Motor division of PNS is divided into:
A
Somatic motor division: Carries signals to skeletal muscles
Autonomic nervous system: Carries signals to smooth muscle, cardiac muscle and glands
EFFERENT!!!!!
6
Q
Neuroglial cell types of the CNS
A
Astrocytes
Oligodendrocytes
Microglial cells
Ependymal cells
7
Q
Astrocyte functions
A
Anchor neurons and blood vessels
Regulate the extracellular environment
Facilitate the formation of the BBB
Repair damaged tissue
CNS!!
8
Q
Oligodendrocyte function
A
Myelinate certain axons in the CNS
9
Q
Microglial cells function
A
Act as phagocytes in the CNS
10
Q
Ependymal cell functions
A
Line cavities
Cilia circulate fluid around the brain and spinal cord
Some secrete CSF
CNS
11
Q
Neuroglial cell types of the PNS
A
Schwann cells
Satellite cells
12
Q
Schwann cell functions
A
Myelinate certain axons in the PNS
13
Q
Satellite cell function
A
Surround and support cell bodies in the PNS
14
Q
Dendrites
A
Receive signals and carry information to cell body
DO NOT GENERATE ACTION POTENTIALS
15
Q
Cell body
A
AKA Soma
Contains nucleus, mitochondria and other organelles
16
Q
Clusters of cell body in CNS are called…
A
Nuclei
17
Q
Clusters of cell bodies in PNS are called…
A
Ganglia
18
Q
Axon
A
Carries information away from cell body toward other cells (anterograde and retrograde axonal transport)
19
Q
Clusters of axons in CNS are called…
A
Tracts
20
Q
Clusters of axons in PNS are called…
A
Nerves
21
Q
A membrane potential can trigger and action potential in what part of the nerve cell?
A
Axon hillock
22
Q
Myelin sheath in CNS
A
Insulating layer around a nerve fiber
Oligodendroyctes in CNS can wrap around multiple axons
NO neurolemma
23
Q
Nerves that are typically myelinated are…
A
Those found in muscle tissue, CNS and reflex arcs - need to have FAST conduction. Most motor nerves (efferent).
24
Q
Nerves that are typically unmyelinated include…
A
Most sensory nerves (afferent)
25
Electrical synapses
Presynaptic and postsynaptic neuron
Axolemmas are nearly touching - bridged by gap junctions
Gap junctions create precisely aligned channel pores
Bidirectional
Instantaneous
Cardiac myocytes and some CNS (most are chemical though)
26
Chemical synapses
Presynaptic and postsynaptic neurons
MOST COMMON
Electrical signal --> chemical signal --> electrical signal
Synaptic vesicles containing neurotransmitters (40+)
Neurotransmitter receptors are linked to ion channels in postsynaptic tissue
Synaptic delay
UNIDIRECTIONAL
Signal can vary depending on neurotransmitter
27
Chemical synapse steps (4)
1. An action potential in the presynaptic neuron triggers Ca2+ channels in the axon terminal to open
2. Influx of Ca2+ causes synaptic vesicles to release neurotransmitters into the synaptic cleft
3. Neurotransmitters bind to receptors on the postsynaptic neuron
4. Ion channels open on postsynaptic tissue, leading to a local potential and possible an action potential
28
Presynaptic control is done by...
Regulatory neurons: facilitate of inhibit presynaptic activities by affecting the membrane of the cell body or sensitivity of axon terminals.
This is independent of what the dendrite is doing. Directly affects membrane potential of the cell body itself independent of what the dendrites are bringing in.
Can also directly affect how strong the AP is at the axon bouton and can change how much electrical signal/neurotransmitter is transmitted to the post-synaptic tissue.
The regulatory neuron directly affects the presynaptic neuron but ultimately is going to determine how strong of a signal the postsynaptic tissue receives.
29
Presynaptic inhibition is done via:
GABA
Inhibitory neuron releases GABA
GABA prevents voltage-gated calcium channels from opening in the presynaptic neuron which decreases the transmission of the signal
Less/no neurotransmitter is released and therefore the threshold is not reached in the postsynaptic neuron
30
Termination of neurotransmitter release (3)
1. Diffusion and Absorption: Neurotransmitters diffuse away from the synaptic cleft and are returned to the presynaptic neuron
2. Degradation: Neurotransmitters are degraded by enzymatic reactions in the synaptic cleft.
Cholinesterase terminates signal at motor end plate
3. Reuptake: Neurotransmitters are taken back into the presynaptic neuron
31
Ionotropic vs Metabotropic Receptors
Postsynaptic neurotransmitter receptors - same result but take a different path to get there.
Ionotropic receptor: Neurotransmitter binds to receptor site and the ionotropic receptor/ion channel opens
Metabotropic receptor: Neurotransmitter binds to the metabotropic receptor that is SEPARATE from the ion channel. the receptor is associated with an inactive G protein intracellularly that is activated when the neurotransmitter binds the metabotropic receptor. This causes in increase in second messengers which opens the ion channel.
32
How can sensory receptor be classified?
By the location of the stimuli they detect
and
by the type of stimuli that causes them to depolarize and generate a receptor potential
33
Sensory receptor types classified by the location of stimuli they detect (3)
Exteroreceptors: usually close to body's surface; detect stimuli originating from OUTSIDE the body
Interoreceptors: usually found within body's interior; detect stimuli originating from INTERNAL ORGANS
Proprioceptors: detect position and load
34
Sensory receptor types classified by the type of stimuli that causes them to depolarize and generate a receptor potential (5)
Mechanoreceptors: depolarize in response to anything that MECHANICALLY DEFORMS tissue where receptors are found - mechanically gated ion channels
Thermoreceptors: exteroceptors, most of which are slowly adapting receptors; depolarize in response to TEMPERATURE CHANGES. Separate receptors to detect hot and cold.
Chemoreceptors: can be either interoceptors or exteroceptors. Depolarize in response to binding to SPECIFIC CHEMICALS (in body fluids or in air); generate a receptor potential as sodium ion channels open. TASTE/SMELL
Photoreceptors: special sensory exteroceptors found ONLY in the eyes. Depolarize in response to LIGHT
Nociceptors: usually slowly adapting exteroceptors - some interoceptors. Depolarize in response to NOXIOUS STIMULI
35
Biogenic amine neurotransmitters include:
Catecholamines (norepinephrine, epinephrine, dopamine)
Serotonin
Histamine
36
Amino acid transmitters include:
Glutamate (excitatory)
GABA
Glycine
37
Neuropeptide neurotransmitters include:
Substance P (pain perception)
Opioids (pain control)
Neuropeptide Y
All excitatory and inhibitory, and all metabotropic
38
Major neurotransmitter of the body
Acetylcholine (excitatory)
Ionotropic and metabotropic
39
Membrane potentail occurs due to...
asymmetrical ion distribution across a selectively permeable membrane; non equilibrium and steady-state (flux)
Diffusion potential
40
Ions that affect membrane potential include:
Na+
Cl-
Ca2+
K+ (higher concentration inside the cell)
41
Vm stands for:
Membrane potential
42
Na+ units, plasma concentration and cell concentration
Units: mmol/L
Plasma conc: 142
Cell conc: 15
43
K+ units, plasma concentration and cellular concentration
Units: mmol/L
Plasma conc: 4.4
Cell conc: 140
44
Ca2+ units, plasma concentration, cellular concentration
Units: mmol/L
Plasma conc: 1.2
Cellular conc: 100 nM (VERY SMALL)
45
H+ units, plasma concentration and cellular concentration
Units: pH
Plasma conc: 7.4
Cell conc: 7.2
46
When talking about plasma and cellular ion concentration, we are talking about...
Unbound ions ONLY! Others are bound to albumin and those do not matter in terms of membrane potential.
47
Cl- units, plasma concentration and cellular concentration
Units: mmol/L
Plasma conc: 102
Cell conc: 10-20
48
HCO3- units, plasma concentration and cellular concentration
Units: mmol/L
Plasma conc: 24
Cell conc: 10-16
49
Protein units, plasma concentration and cellular concentration
Units: g/dL
Plasma conc: 7
Cell conc: 30-40
50
Glucose units, plasma concentration and cellular concentration
Units: mg/dL
Plasma conc: 100
Cell conc: --
51
Osmolality units, plasma and cellular concentration
Should be the same inside and outside the cell!
Units: mosmol/kg H2O
Plasma conc: 290 (300)
Cell conc: 290 (300)
52
T/F: Every cell is excitable
False: Distribution of ions is the same in every cell but not every cell is excitable. Excitable cells are excitable because certain ions are allowed through the cell membrane (either in or out).
53
Excitable cell types can QUICKLY AND SELECTIVELY alter...
membrane permeability for ions.
54
Permeability changes are due to...
coordinated opening and closing of ion channels.
55
Excitable cells use ___ and ___ as a means of signaling or initiating intracellular events.
Changes in Vm and transmembrane ion fluxes
56
Sensory cell examples and how they transduce sensory stimuli
Mechanoceptors, olfactory receptors and photoreceptors
By generating a Vm change called a receptor potential
57
Nerve cells signal to each other and to effector tissues by using...
Action potentials
58
How to myocytes and secretory cells facilitate contraction and secretion, respectively?
Use a change in Vm to increase intracellular Ca2+ concentrations
59
Classification of ion channels include (3):
Selectivity
Voltage dependence
Gating
60
Ion channel classification by selectivity
Basically ion channels (Na, K, Ca, Cl, etc)
Generally very selective, but not always!
61
Ion channel classification by voltage dependence
Present in electrically excitable tissue (nerve, muscle)
They open or close in response to Vm
Affects the probability of the channel being open or closed
Open/closed state is not black and white!!!!
62
Ion channel classification by gating
Channels do not open for the same length of time, even "similar" channels like Ca2+ channels.
Channels may have burst activity followed by quiescence.
63
T/F: Ion channels require metabolic energy
FALSE - no metabolic energy is required by ion channels
64
T/F: The ion channel determines direction of flow
FALSE: the electrochemical gradient determines the direction of flow
65
Ion channels are very selective to:
Ionic charge: anion vs cation
Cl- is really the only negatively-charged ion that can pass through anion selective channels
Bicarbonate is negatively charged but is too large to pass through these channels
66
Cation selective channels generally allow how many ion species to pass through?
Generally 1 but there are exceptions:
L-glutamate activation of N-methyl-D-aspartic acid (NMDA) receptor which allows both Na+ and Ca2+ to pass through
67
Example of a ligand preventing an ion from passing through its ion channel
Phencyclidine (PCP) binds to and blocksthe NMDA channel preventing Na+ and Ca2+ from passing through
68
Non-gated ion channels
Open most of the time
Control flow of ions during resting membrane potential
Leak channels!!!!!!!!! Na+ and K+. Will focus more on potassium leak channels in this course
69
Gated ion channels
All are allosteric proteins!! Exist in more than one conformation
They exist in open OR closed state, at least
At rest they are usually closed
They open in response to stimuli (voltage change, ligand, etc)
Voltage gated exist in 3 states (typically): Rest (closed), active (open), refractory (inactivated)
70
States of ion gated channels and voltage gated sodium channel example
Resting (closed): Activation gate is closed
Activated (open): Activation gate is open allowing ions through channel
Inactivated (refractory): Inactivation gate is closed
When activation gate is closed, sodium can not pass from the extra to intracellular space through the channel. When there is a change in membrane potential at the site of the pore, the activation gate open allowing Na+ to pass into the cell. When we reach a certain membrane potential, the inactivation gate will close no longer allowing Na+ to pass through the channel, but the channel/ion pore itself is not closed because the activation gate remains open - it is simply inactive.
71
"Certain cells, including neurons and myocytes, have a property called _______________... ________ above a certain _______ voltage triggers a spontaneous all-or-none response called and _________.
Electrical excitability
Threshold
Action potential
72
Action potentials
Transient, regenerative electrical impulse in which Vm rapidly rises about 100 mV (not TO 100 mV, but rises 100 mV total)
Can propagate long or short distances
Brain/CNS receives AP from peripheral sensory organs, generates efferent AP to effector organs (i.e. skeletal muscle)
73
Electrical currents in cells
In cells, current moves across the membrane and is mediated by movements of Na+, K+, Ca2+, Cl- and HCO3-.
Ion movements are mediated by ion channels, electrogenic ion transporters and pumps.
74
Ohm's Law
Electrical currents across cell membranes
I = V/R OR V = IR
I = current, V = voltage, R = resistance
75
Ohm's Law/Current for CV system
F = P/R OR F = (change)P/R
I = gV
F = flow and is equivalent to current
P = pressure
R = resistance
g = conductance
V = voltage
76
Ions
Electrically charged atoms
Cations (+)
Anions (-)
77
Influx of ions
Ionic flow INTO a (nerve) cell
78
Efflux of ions
Ionic flow OUT of a neuron
79
Electrical current
Movement of electrical charge (amps)
Depends on electrical potential and conductance (1/R)
80
The higher the voltage difference from one side of the membrane to the other, the ________ the current provided the _____ remains constant.
greater
resistance
The same goes for blood flow.
81
Electrical potential
Voltage (volts)
Difference in charge b/w the anode (+ pole) and the cathode (- pole)
More current flows when voltage is increased provided the resistance is held constant!!!
82
Electrical conductance
The ability of an electrical charge to move from one point to another (Siemens - unit of choice)
Inverse of resistance (Ohms)!!!
83
Direction of current flow is determined by:
Historically by the direction of NET cation flow
84
Inward current describes ______ flowing into the cell (neuron)
Cations
85
Outward current describes ______ flowing out of the cell (neuron)
Cations (and anions flowing INTO the cell)
86
Leakage current is the flow of ions through ______ _________.
Non-gated channels
87
Membrane potential definition
Vm
Electrical potential difference across a membrane at any given time
88
Resting membrane potential
Resting Vm
Vm of a membrane when not generating and action potential
89
Resting Vm of CNS neuron is typically:
-65 mV
90
Chloride flowing into a cell will produce an _______ current.
Outward current because current is described by the direct that cations are moving. If chloride anions are moving into the cell then cations will be moving out of the cell
91
Depolarization
reduction of (-) charge inside the cell
Ex: -65 to -50
Depolarization makes the cell less negative. The voltage difference b/w the inside and outside of the cell becomes less and moves closer to zero
92
Hyperpolarization
Increased (-) charge inside the cell
Ex: -65 to -70
Makes the cell more negative with respect to the outside of the cell. Vm moves further from zero in the negatives
93
Threshold potential
Vm at which sufficient voltage gated Na+ channels are open that can generate an AP
Relative permeability of Na+ exceeds K+
AP is generated beyond threshold
94
Ionic basis of membrane potential
Ions are symmetrically distributed across the cell membrane - this generates a membrane potential.
95
Membrane potential
Difference in electrical potential between intra and extracellular spaces
Vm (or Vrm) is typically -90 mV in RESTING skeletal muscle, alpha motor neurons, and -65 in CNS
Interior of the cell is more negative than exterior!!!
96
Which is more negative in terms of resting Vm: inside of outside of the cell
Inside!!
97
Resting Vm for skeletal muscle and alpha motor neurons
-90 mV
98
Resting Vm of CNS neurons
-65 mV
99
Nernst equation
The electromotive force (EMF) = Nernst potential
EMF (millivolts) = +/- 61 x log (concentration inside/concentration outside)
100
What happens when the membrane becomes permeable to a particular ion?
The ion is going to move in or out of the cell (according to electrochemical gradient) and change the membrane potential (Vm) toward its own equilibrium potential.
101
The Nernst equation calculates equilibrium potential based on ....
the ion's intracellular and extracellular concentrations.
If ion concentrations change then the equilibrium potential changes.
102
If the membrane becomes permeable to a particular ion, the ion is going to move in or out of the cell and change...
the resting membrane potential (Vm) towards its own equilibrium potential
103
Potassium equilibrium potential is ________ relative to Vm.
NEGATIVE.
If K+ permeability increases (K+ channels open), then K+ flows out of the cell and makes Vm more negative.
104
Sodium equilibrium potential is ________ relative to Vm.
POSITIVE
If Na+ permeability increases, (Na+ channels open) and Na+ flows into the cell making Vm more positive.
105
Sodium equilibrium
ENa = +61 mV
106
Potassium equilibrium
EK = -90 mV
Potassium will flow out of the cell until Vm reaches -90, and the electrical gradients equilibrate.
107
Calcium equilibrium
ECa = +120 mV
108
Goldman equation
Looks at all ions at play (Nernst equation only looks at one ion at a time).
It allows you to figure out the instantaneous membrane potential at any given moment because it include ion concentration and permeability for each individual ion.
109
In quiescent tissue, the Goldman equation gives...
Resting membrane potential because P is always nearly zero
110
Determination of resting membrane potential
Electrochemical (net) driving force = Vm - Ex
111
When the Nernst potential for an ion is less than what the membrane potential is, the ion flows ______ of the cell when the membrane becomes permeable to the ion.
OUT OF THE CELL
112
When the Nernst potential for an ion is greater than the membrane potential, the ions flow _____ of the cell when the membrane becomes permeable to the ion.
INTO THE CELL
113
Inside/outside of the cell are negative or positive?
Inside = negative
Outside = positive
114
At rest the inside of a cell is always ______ (negative or positive) with respect to the ECF.
Negative
115
When a positively charged ion (cation) flows into a cell (influx), the membrane loses ___________.
Polarization
116
During depolarization, Vm becomes less _________.
NEGATIVE.
By convention an upward deflection on a voltage record.
117
During hyperpolarization, Vm becomes more ________.
NEGATIVE
Downward deflection on a voltage record.
118
During hyper polarization, cations leave (efflux) the cell and Vm becomes more _______ and the membrane becomes more __________.
NEGATIVE
POLARIZED
119
When positive charges flow into the cell, they generate an _______ current. By convention, these currents cause a _________ deflection.
Inward
Downward
Currents typically more in the opposite direction than Vm.
120
Positive charges leaving the cell cause an ________ current and an ________ deflection on a recording device
Outward
Upward
Currents typically move in the opposite direction than Vm.
121
Depolarization/repolarization/hyperpolarization is referring to...
membrane potential (Vm)
122
Current and membrane potential deflections are
opposite from one another.
123
Membrane potential changes definitions
All relative to resting potential:
Depolarization (Above threshold/resting potential)
Overshoot (Above 0 mV)
Repolarization (back down to resting potential)
Hyperpolarization (below resting potential)
124
What makes neurons excitable and gives them the ability of generate an action potential?
The density of voltage gated Na+ channels
125
Excitable cells exhibit two distinct types of electrical behaviors:
1. Local graded potentials
2. Far-traveling action potentials (all or nothing)
126
If the Na+ channel density is not sufficient, membrane is only capable of generating....
local currents that die out as you move further from the source.
127
Types of local (graded) potentials
Hyperpolarizing graded potentials (becoming more negative) caused by opening of K+ or Cl- channels
Depolarizing graded potentials (becoming less negative) caused by opening of Na+ channels
128
Graded/local action potentials will always remain below...
Threshold
129
Examples of graded potentials
Sensory receptor potentials - pushing harder on your skin will generate a larger graded potential
Dendritic postsynaptic potentials in CNS: depends on what is feeding into the cell at that time
130
Local currents/graded potential magnitude is proportional to...
the number of open channels. The amplitude is graded with input intensity and are minor membrane events.
They can summate in space and time -- depending on the magnitude and direction, they can generate a greater change or cancel each other out.
Vm change is limited and ONLY spreads locally
131
The strength of the stimulus for a graded potential is encoded in the _______ of the graded potential.
amplitude
132
Graded potentials have limited reach due to ________ __________.
Electrotonic conduction (potential dies out further from source?)
133
Graded potentials have limited reach due to ....
leak channels. The intensity of the stimulus decreases with distance (decremental conduction).
Leakage of charge (predominantly K+) across the plasma membrane reduces the local current at sites farther along the membrane from the site of initial depolarization.
134
Decremental conduction is:
when the intensity of the stimulus decreases with distance.
135
There is a membrane potential change where the is/isn't myelin sheathing?
Where there is NOT myelin sheathing - nodes of Ranvier
136
Why isn't there a change in membrane potential where myelin sheathing is present?
There is no way for ions to access intra or extracellular space. The K+ leak channels are covered by myelin.
137
Unmyelinated axon APs die out because...
K+ leak channels leak current out of the cell.
138
The size principle of nerve fibers
Larger diameter fibers conduct at higher velocities
This is because of membrane resistance vs axonal cytoplasm resistance
Larger fibers have lower resistance vs small fibers
Larger fibers have lower cytoplasmic resistance relative to membrane resistance
139
Graded potential signal is encoded in the ...
Amplitude
140
Action potential signal is encoded in the...
frequency
141
Graded potentials occur in what type of cells?
Excitable and non-excitable
142
Action potentials occur in what type of cells?
Excitable cells only!!!! Do not occur in non-excitable cells like graded potentials
143
Are action potentials depolarizing and hyperpolarizing?
No - only depolarizing!
Graded potentials are depolarizing and hyperpolarizing
144
Graded potentials have ______ amplitudes.
Varying.
Action potentials are always the same amplitude - all or nothing!
145
Graded potentials vs action potentials for signal conduction
Graded = electrotonic conduction
AP = regenerative signal propagation
146
What does it mean when we say the signal is encoded in the amplitude of graded potentials?
The hyperpolarization/deplolarization amplitude size determines the effect
147
Frequency is measured in...
hertz
148
What is the principal mechanism of nerve impulse propagation and transmission?
Action potentials
149
Action potentials are explosive membrane events that are a set _________ no matter how often it's depolarized.
amplitude
150
Action potentials are always ________ meaning that they are due to the opening of ____ ______.
Depolarizing
Na+ channels
151
Action potentials are self ________
propagating
The same type of AP regenerates along the route of conduction - runs the same amplitude the entire length of muscle fiber or nerve fiber
152
Phases of an action potential
1. Upstroke (depolarization)
2. Overshoot (when membrane potential is positive)
3. Downstroke (repolarization) and after the Vm goes below 0 again
4. Afterpotential (after hyperpolarization) when membrane potential is more negative than resting membrane potential (RMP,Vm)
Then returns to resting membrane potential.
153
What occurs during depolarization of an AP?
Voltage gated Na+ channels open allowing in influx of Na+ ions into the cell - increased membrane conductance to sodium ions.
154
What happens during repolarization of an AP?
There is an increase in K conductance when K+ gates open allowing an efflux of K+ out of the cell.
155
What occurs at the peak of the action potential?
It reaches a voltage that closes voltage gated Na+ channels and opens voltage gated K+ channels. These have already begun to open prior to repolarization.
156
PNa/PK and significance
Conductance of sodium relative to potassium.
As we raise this ratio (essentially increasing sodium conductance/permeability of the membrane to Na), the membrane potential increases
157
What happens with the ratios Na/K conductance is zero?
As we increase EC K concentration, the membrane potential becomes less negative/increases.
RESTING MEMBRANE POTENTIAL INCREASES WITH INCREASED EXTRACELLULAR K CONCENTRATION. PARTICULARLY WHEN THE NA/K CONDUCTANCE IS ZERO.
158
What causes the membrane potential changes during an action potential?
Na influx and K efflux
159
What occurs during the upstroke/depolarization?
An increase in Na+ conductance (and lack of K+ conductance) leads to Na+ rushing into the cell (influx) and moves the membrane potential towards its very positive equilibrium (ENa+)
160
What happens during the downstroke/repolarization?
An increase in K+ conductance (and diminishing Na+ conductance) leads to K+ rushing out of the cell (efflux) and moves the membrane potential towards its very negative equilibrium potential (EK+)
161
Vm and Vna or Vk relationship during AP
Depolarization: Na+ open and Vm moves toward VNa
Overshoot: Na+ channels inactivate and Vm moves back toward Vk
Repolarization: K+ channels open and Vm moves faster toward Vk
Hyperpolarization: Na+ channels deinactivated, K+ channels open, Vm moves close to Vk
162
Phases of an action potential beginning with resting (5)
1. Resting state: The activation gates on the Na+ and K+ channels are closed, and the membrane's resting potential is maintained
2. Depolarization: A stimulus opens the activation gates on some Na+ channels. Na+ influx through those channels depolarizes the membrane. If the depolarization reaches the threshold, it triggers an AP.
3. Rising phase of the AP: Depolarization opens the activation gates on most Na+ channels, while the K+ channels' activation gates remain closed. Na+ influx makes the inside of the membrane positive with respect to the outside.
4. Falling phase of the AP: The inactivation gates on most Na+ channels close, blocking Na+ influx. The activation gates on most K+ channels open, permitting K+ efflux which again makes the inside of the cell negative.
5. Undershoot: Both gates of the Na+ channels are closed, but the activation gates on some K+ channels are still open. As these gates close on most K+ channels, and the inactivation gates open on Na+ channels, the membrane returns to its resting state.
163
Subthreshold potentials only elicit...
graded/local potentials
164
The peak of an AP is shaped by...
the ionic movements in and out of the cell, and how long it takes to do that.
The density of ionic channels determines the slope and peak of an AP
165
How does resting membrane potential change with respect to EC K+ concentrations?
Resting Vm changes if extracellular K+ concentration changes (because K+ conductance is high even at rest).
Increased EC K+ will increase resting membrane potential. This brings Vm closer to threshold meaning that we will need a small stimulus to elicit an AP. This makes it easier to depolarize tissues.
Decreased EC K+ will decrease resting membrane potential. This brings Vm further from threshold meaning that we will need a stronger stimulus to elicit an AP. This makes it more difficult to depolarize tissues.
166
Hypokalemia will lead to ...
Muscle weakness - brings Vm further from threshold making it more difficult/need a stronger AP to elicit an AP.
167
Increasing/decreasing ____ conductance can alter membrane potential.
K+
Increasing K+ conductance causes K+ to leave the cell resulting in hyperpolarization of the cell because we are decreasing membrane potential.
Decreasing K+ conductance causes K+ to stay in the cell.
This is DIFFERENT than manipulating EC K+ concentrations. The number of ions needed to move out of the cell for repolarization will never affect the EC K concentrations enough because the number is relatively small compared to EC K+ levels.
168
Increasing K+ conductance (g) results in:
K+ leaving the cell resulting in hyperpolarization. Recall that increasing g for an ion causes the Em to move toward the equilibrium potential for that ion. Thus, the cell will move from -70 mV to -95mV.
169
Decreasing K+ conductance (g) results in:
depolarization of the cell - the cell moves away from K+ equilibrium.
170
Which changes the EC K+ concentration - K+ leak channels or voltage gated K+ channels?
K+ leak channels!!!
increasing permeability of the membrane to K+ by opening voltage gated K+ channels will not have an effect on EC K+ concentrations.
171
Is conductance the same as EC K+ concentrations?
NO -they are not the same!!!!!!!!
172
Hypokalemia
Decreased EXTRACELLULAR K+ concentration
This HYPERPOLARIZES the membrane
Vm is decreased - moves closer to Vk (-95)
Makes depolarization more difficult and a larger depolarizing current will be required
Can lead to asystole (failure of contraction)
173
Hyperkalemia
Increased EXTRACELLULAR K+ concentration
The membrane is "depolarized"
Vm is increased - moves farther away from Vk and closer to VNa
Makes it easier to initiate an AP. Once an AP is fired, it may not be able to repolarize. This is because if resting membrane potential is too high then it may never get low enough for enough K+ channels to open to repolarize the cell. May also never move the Na+ channel from inactive to closed.
174
What will happen when you decrease EC Na+ concentrations?
This will change the AP peak.
Decreasing EC Na+ concentrations will produce an AP with a smaller peak.
Increasing EC Na+ concentrations will produce an AP with a larger peak because there is more sodium to rush into the cell causing in increase in Na+ conductance.
175
Which has a more significant effect on the cell - changing EC Na+ or EC K+ concentrations?
K+ concentration because the scale is much smaller so making smaller changes to K+ has a larger effect than make the same change to Na+ concentrations
176
Which has refractory periods - Graded potential or action potential?
Action potentials. Graded potentials DO NOT have refractory periods.
177
Which can be summed - graded or action potentials?
Graded - AP can NOT be summed.
178
What are action potentials initiated by? Graded potentials?
AP: Graded potentials
Graded potentials: environmental stimulus (receptor), by neurotransmitter (synapse) or spontaneously.
179
Graded potentials and AP depend on what types of mechanisms?
Graded: ligand-gated ion channels or other chemical or physical changes
AP: voltage-gated ion channels
180
Absolute refractory period
Due to inactivated Na+ channels. While voltage-gated Na+ channels are inactive but not closed, the cell can NOT produce another action potential.
Axon membrane is incapable of producing another AP NO MATTER HOW LARGE THE STIMULUS IS.
This period lasts just about until the end of repolarization.
181
Relative refractory period
Due to continued outward diffusion of K+.
Once the Na+ channel closes, you can produce another AP, but the stimulus has to be greater.
Voltage gated ion channel shape alters at the molecular level.
Voltage gated potassium channels are open.
Axon membrane can produce another action potential but requires a stronger stimulus.
The stimulus needed to produce an AP is increase initially and eventually will decrease down to normal.
182
Excitability of the cell during refractory periods
Absolute: Zero
Relative: Increasing
Resting: High
183
Most Na+ channels are __________ during an absolute refractory period.
Inactivated!!
184
Some Na+ channels are still ______ and most K+ channels are _______ during a relative refractory period.
Inactivated
Open
185
Changes in plasma Ca2+ change _____ _____ of excitable cells.
membrane excitability
186
Hypocalcemia
Decreased plasma Ca2+ concentrations leading to INCREASED excitability.
This increases THRESHOLD!!!!
Spontaneous alpha MN firing --> spasm (tetanus)
Cardiac arrhythmias
Seizures
187
Hypercalcemia
An increase in plasma Ca2+ concentrations leading to DECREASED membrane excitability.
This decreases THRESHOLD!!!
CNS depression and coma
Decreased myocardial excitability (anti-arrhythmogenic effect)
188
Plateaus in action potentials occur when...
repolarization does not begin immediately following depolarization. Occurs because calcium (and Na) is coming into the cell at the same time that K+ is leaving the cell. These can occur in the cardiac myocyte.
189
The causes (2) of a plateau in an action potential are:
1) Depolarization occurs because of the opening of voltage-gated sodium channels (fast) and the secondary opening of calcium-sodium channels (slow). The Ca/Na channels prolong the depolarization time as positively charged Ca flows into the interior of the cell.
2) Myocardial voltage-gated potassium channels are particularly slow in opening and are typically not open until the end of the plateau further delaying repolarization.
190
Action potentials in nonneural tissue: skeletal muscle
The AP in skeletal muscle is similar to that of an alpha moron neuron, only slower conducting and longer time to complete a cycle.
191
Action potentials in nonneural tissue: cardiac myocytes
The AP in cardiac myocytes is generally similar to that of an alpha MN, but has a plateau due to Ca2+ coming into the cell (depolarization) at the same time that K+ is leaving the cell.
The AP of a cardiac nodal cell is different still.
192
The ANS is primarily responsible for managing what?
phasic/acute deviations of homeostasis.
193
The endocrine system is primarily responsible for managing what?
more chronic/permanent management of homeostasis.
It can respond phasically particularly at the prompting of the ANS - norepinephrine stimulates the adrenal glands to release epinephrine
194
Information from the brain travels via (2)
Somatic motor neurons to skeletal muscle
Autonomic neurons innervating smooth muscle, cardiac muscle, secretory epithelia and glands
195
Three divisions of the ANS
Parasympathetic (PANS)
Sympathetic (SANS)
Enteric nervous system (ENS): Also called the "little brain" and specific to the digestive tract
196
Are ANS branches weighted equally in each organ/organ system?
No! Some have more or predominant input from one branch or the other. Ex: the SANS causes blood vessels to constrict. When they are dilated it doesn't mean that there is more parasympathetic drive than sympathetic. It just means there is less sympathetic drive. Same with the GI system and parasympathetic input.
197
Parasympathetic effects on organs/systems:
Pupillary constriction
Tear secretion
Airway constriction
Slows heartbeat
Stimulates digestion
Stimulates gallbladder to release bile
Stimulates GI function
Contracts urinary bladder
Relaxes urinary sphincter
Induces penile erection
Induces engorgement and secretions of female genitalia
198
Sympathetic effects on organs/systems:
Dilates pupil and elevates eyelid
Ciliary body
Stimulates salivation
Modulates blood vessel tone
Relaxes airways
Causes erection of hair
Stimulates secretion by sweat glands
Accelerates and strengthens heartbeat
Inhibits digestion
Stimulates glucose production and release from liver
Stimulates secretion of epinephrine
Inhibits GI function
Relaxes urinary bladder
Contracts urinary sphincter
Induces ejaculation
Stimulates contraction of smooth muscle in female genitalia
199
Primary neurotransmitter of SANS
Norepinephrine (stimulates epinephrine release from adrenal glands)
200
Primary neurotransmitter of PANS
Acetylcholine
201
What can change the effect of ANS input in an organ system?
The amount of neurotransmitter can have different effects in the same organ
202
Examples of the same branch of ANS eliciting opposite effects in different organ systems
In vasculature, norepinephrine and epinephrine cause constriction. In the lungs they cause dilation. This is because the same neurotransmitter is binding to different receptors in different tissues eliciting different effects.
203
Which systems have sympathetic input ONLY (2)?
Vascular smooth muscle cells - vasoconstriction
Sweat glands - secretion
204
Which organ has parasympathetic input ONLY?
Stomach - stimulates acid secretion
205
Sympathetic/parasympathetic effects on the SA/AV nodes
Parasympathetic: Decrease HR
Sympathetic: Increase HR
206
Sympathetic/parasympathetic effects on cardiac muscle
Parasympathetic: Decrease (atrial) contractility
Sympathetic: Increase contractility
207
Sympathetic/parasympathetic effects on the lung smooth muscle cells
Parasympathetic: constriction
Sympathetic: dilation
208
Sympathetic/parasympathetic effects on the pancreas
Parasympathetic: Increases secretion
Sympathetic: Decreases secretion
209
Sympathetic/parasympathetic effects on the GI tract
Parasympathetic: increase motility & sphincters relax
Sympathetic: decrease motility & sphincters contract
210
Somatic nervous system target organ, neurotransmitter and receptor
Skeletal muscle
Acetylcholine
N1 (nicotinic acetylcholine receptor)
211
Norepinephrine binds which type of receptors?
alpha and beta adrenergic receptors
212
Acetylcholine binds which type of receptors?
N1 (nicotinic) and muscarinic Act receptors
213
Parasympathetic target organ, neurotransmitters and receptors
Preganglionic fiber synapses at N2 receptor via acetylcholine
Postganglionic fiber synapses at M (muscarinic acetylcholine) receptor innervating smooth muscle, cardiac muscle and glands.
214
Which nicotinic receptors does the ANS use?
N2 receptors (with acetylcholine) - preganglionic fiber synapse
215
Which nitotinic receptor does the somatic nervous system use?
N1 with acetylcholine on skeletal muscle
216
Sympathetic neurotransmitters, receptors and target organs
Norepinephrine: preganglionic fiber synapses at N2 receptor in ganglion releasing acetylcholine. Post ganglionic fiber synapses at alpha/beta receptors using norepinephrine
Epinephrine: preganglionic fibers synapse at N2 receptors of chromaffin cells of adrenal glands using acetylcholine. This causes release of epinephrine that travels through the blood to reach target cells using alpha/beta adrenergic receptors.
217
Acetylcholine binds what types of receptors?
Nicotinic (N1 and N2) and muscarinic receptors
218
Epinephrine will bind what receptors most preferentially?
Beta adrenergic receptors
219
Norepinephrine will bind which receptors more preferentially?
Alpha adrenergic receptors
220
As norepinephrine increases, it will also stimulate release of more....
epinephrine via the adrenal gland stimulation
221
Epinephrine receptor selectivity, high and low dose-dependent actions
Receptor: B1 = B2 > a1 = a2
Low dose: cardiac stimulation, vasodilation, bronchodilation
High dose: greater cardiac stimulation, vasoconstriction, bronchodilation
222
Norepinephrine receptor selectivity, high and low dose-dependent actions
Receptor: a1 = a2 > B1 = B2
Low dose: some cardiac stimulation, vasoconstriction
High dose: Reflex bradycardia and extensive vasoconstriction
223
Dopamine receptor selectivity, high and low dose-dependent actions
Receptor: B1 = B2 > a1
Low dose: cardiac stimulation, vasodilation
High dose: vasoconstriction
224
Degradation of norepinephrine and epinephrine
1. 50-80% reuptake
2. Diffusion (into blood)
3. MAO or COMT in heart, glands, smooth mm cells
225
Muscarinic receptors are primarily found in the _______ nervous system.
Parasympathetic (but M1 are also found in sympathetic postganglionic neurons)
226
M1 receptor location, second messenger/cascade and action
Location: CNS and sympathetic postganglionic neurons
Second messenger/cascade: Form IP3 and DAG, increase intracellular calcium concentrations
Action: Cellular excitation
227
Potassium channels are always hyperpolarizing except for in the _______.
Pancreas
228
M2 receptor location, second messenger/cascade and action
Receptor location: Cardiac and coronary smooth muscle
Second messenger/cascade: Open K+ channels, inhibits adenylyl cyclase and reduce cAMP
Action: hyperpolarization, vasodilatory effects on coronary smooth muscle cells
229
M3 receptor location, second messenger/cascade and action
Receptor location: glands and visceral smooth muscle, vascular smooth muscle
Second messenger/cascade: Form IP3 and DAG, increase intracellular calcium concentrations
Action: Secretion and contraction, relaxation
230
Sympathetic vs parasympathetic
Never "all or none"
More of which is predominating at any given point in time.
Heart rate is predominantly one or the other
Cardiac output are regulated BEAT TO BEAT
In arterioles VSMCs vasodilation is really a decreased sympathetic tone
GI tract has a lot of parasympathetic input (probably the most of the entire body), but sympathetic control is massive, particularly regarding arterioles.
231
Another name for neuromuscular junction is...
Motor end plate
232
The motor end plate/NMJ is...
the synaptic connection between the alpha motor neuron axon and the skeletal muscle fiber
233
What is the most studied synaptic connection?
The NMJ/neuromuscular junction
234
Which part of the motor end plate has invaginations? Why?
The muscle fiber at the NMJ. To increase the surface area for acetylcholine receptors
235
Sarcolemma is the...
postsynaptic membrane of the NMJ. Folded to increase surface area for AchR
236
What prevents the NMJ from sliding away from one another?
The presynaptic bouton is anchored to the postsynaptic membrane by the ECM (proteins and proteoglycans). These two things NEVER touch but need to stay close to one another for synaptic transmission.
237
Events at the NMJ
1. Neurotransmitter (Ach) is packaged into vesicles transported to presynaptic terminal
2. AP arrives at the presynaptic terminal
3. Depolarization of nerve membrane at presynaptic terminal OPENS voltage gated Ca2+ channels
4. Increased presynaptic Ca2+ concentration triggers fusion of vesicles to the presynaptic membrane and release of neurotransmitter (QUANTA) into synaptic cleft. About 150 quanta per vesicle.
5. Neurotransmitter (Ach) molecules diffuse across the synaptic cleft and bind to specific (Act) receptors on the postsynaptic cell.
6. Binding of neurotransmitter (Ach) to (Ach) receptor activates postsynaptic cell. 2 Ach/AchR at NMJ for activation of AchR
7. Termination of process: 1. Enzymatic destruction of neurotransmitter. 2. Uptake of neurotransmitter by presynaptic cell of other cells (usually Na+ mediated). 3. Diffusion of neurotransmitter away from receptor
238
What type of receptor is the AchR? Inotropic or metabotropic
Inotropic (nicotinic)
239
What type of receptor is a muscarinic receptor? Inotropic or metabotropic?
Metabotropic
240
How many Ach molecules are required for activation of 1 AchR?
2
241
What happens once an AchR is activated by 2 Ach molecules?
The pore on the receptor opens allowing movement of ions through the pore. The Ach receptor is non-specific and Na+ primarily moves into the postsynaptic cell but can also let K+ out (not at the same time)
242
How is an action potential triggered at the motor end plate?
Ach binds to AchR opening the pore and allowing sodium into the muscle cell and potassium out of the muscle cell. This causes a change in the local membrane potential that, if large enough, can cause a change in membrane potential opening voltage gated sodium channels (that are located in the folds of the sarcolemma) depolarizing the cell and triggering an action potential.
243
Thin filaments are
actin
244
This filaments are
myosin
245
Muscle arrangement from largest to smallest
Fascicle ---> fiber ---> myofibril ---> myofilaments ---> thick and thin filaments (repeating units make up the sarcomere)
246
A sarcomere spans from ____ to ____.
Z line to Z line
247
Actin/thin filaments only in a sarcomere are represented by the ______ which spans the _____.
I band
Z line
248
The H band is where there is no _____ overlap with _____.
Actin
Myosin
Right in the middle of the sarcomere
249
The A band...
spans the length of myosin filaments
250
The M band...
Is right in the center of the sarcomere and is where myosin is anchored
251
T tubule location and function
invaginations in the myofibril usually where there are a lot of sarcoplasmic reticulum
It conducts the action potential that is occurring along the surface of the muscle fiber down into the muscle fiber so that it can be depolarized in unison
252
Actin structure and function
Thin filaments
Double stranded alpha helices of F(filamentous) actin.
Contains 2 regulatory proteins: tropomyosin and troponin
253
Tropomyosin structure and function
2 alpha helices that fit in the groove of the actin helix
Regulates the binding of myosin to actin
254
Troponin structure and function
Heterotrimer bound to tropomyosin
Troponin T (TnT): binds to tropomyosin
Troponin C (TnC): binds 2 Ca2+ molecules
Troponin I (TnI): binds actin and inhibits myosin interaction
255
Myosin structure and function
Thick filaments
Made up of heavy chains and light chains
Heavy chains form cross bridge and hydrolyze ATP
Light chains stabilize and regulate ATPase activity (smooth muscle mostly) - located on the hinge region of the heads of the myosin heavy chain
256
Excitation-Contraction Coupling is where you take the ________ from the sarcolemma and produce ______.
Electrical impulse
Work
257
Sarcolemmal resting membrane potential
-85 mV
Some can be closer to -70 mV
258
Why may there be variation in resting Vm in striated muscle fibers?
The diameter of the muscle fiber will affect the Vm
Thinner diameter muscle fiber in motor neurons = higher resting membrane potential
Thicker diameter tends to have much lower (more negative) resting membrane potentials.
259
At what Vm does a sarcolemmal action potential propagate?
-55 mV (this is pretty universal but some texts quote -45 mV)
260
How long does a muscle AP last and how does this compare to a neuronal AP?
Lasts much longer than neuronal AP!
Muscle AP lasts 1-5 ms
Neuronal AP lasts 0.1 ms
261
How fast does muscle AP travel compared to neuronal AP?
Much slower than neuronal!!
Muscle AP travels 3-5 m/sec
Neuronal AP travels 50-130 m/sec for large myelinated neurons
262
What happens after the sarcolemmal AP is initiated?
It propagates along the sarcolemma and into the core of the fiber via transverse tubules (invaginations in the sarcolemma and is still the membrane/conducts AP)
263
What is a triad?
Forms these where the T-tubules interface with the sarcoplasmic reticulum at the A-I juncture on the sarcomere. It is made up of one T-tubule and a SR on either side. Tetrad? called this in lecture but shows triad in the diagram.
264
Where is the DHP receptor located? What does it stand for? What type of receptor is it? What is it connected to? What is its function?
On the sarcolemma in the T-tubule of the muscle cell.
Dihydropyridine receptor
L-type calcium receptor
It is connected to the ryanodine receptor located on the sarcoplasmic reticulum
An action potential causes a conformation shift in the DHP receptor which then causes a conformational shift in the ryanodine receptor allowing calcium to be released from the sarcoplasmic reticulum into the cytoplasm.
265
What happens to the DHP and ryanodine receptor during repolarization?
They return to their original conformation and no more calcium leaves the sarcoplasmic reticulum
266
What form of calcium is released from the sarcoplasmic reticulum?
Ionic/free form which is incredibly biologically active
267
What is calsequestrin?
A protein in the sarcoplasmic reticulum of muscle cells that loosely binds calcium to aid in calcium sequestration in SR.
268
What is SERCA?
A calcium pump found on the membrane of the sarcoplasmic reticulum of muscle cells that pumps calcium from the cytosol back into the SR
269
How does calcium get released from and back into the SR in muscle cells?
It is released in response to depolarization of the muscle cell which changes the conformation of DHP receptor that then causes a conformational shift in ryanodine receptor on SR membrane. This conformational shift in the ryanodine receptor allows calcium to rush out of the SR. After the AP, the SERCA pump pumps calcium back into the SR.
270
What is the DHP receptor inhibited by?
DHP class of drugs for hypertension and arrhythmias
271
What is the ryanodine receptor inhibited by?
A class of plant alkaloids (ryanodine)
272
Excitation Contraction Coupling process
Need an AP to release calcium from SR increasing cytosolic Ca2+ to lead to contraction.
Depolarization of the sarcolemma leads to a shift in conformation of DHPR which leads to a conformational shift in ryanodine receptor causing calcium release from SR.
Ionic calcium is released from the SR causing a 500 fold increase in intracellular calcium concentrations in about 50 milliseconds (only about a 10 fold increase is needed for contraction).
This duration is longer in cardiac myocytes!
2 calcium molecules bind to troponin C that rotates troponin I off of the myosin binding site allowing myosin to bind actin forming a cross bridge and subsequent contraction.
273
What happens if you don't have IONIC calcium to be released from the SR in a muscle cell?
Contraction will cease!!!!
274
Muscle contraction occurs as long as there is ...
ionic calcium present in the cytosol. No calcium = no contraction
275
Why is the "calcium pulse" from the SR releasing 500 fold calcium when only about 10 fold is needed for contraction?
We need ATP for muscle contraction, SERCA pump function. Calcium can also be used to bind enzymes in glycolytic pathway increasing glycolysis and subsequent production of ATP so that we can replace ATP as efficiently as possible during and after muscle contraction.
276
Where do the two calcium molecules bind during muscle contraction?
On troponin C
277
Resequestration by SR during excitation coupling contraction
SERCA pump - ATPase hydrolyses ATP
Concentrates calcium about 10,000 times the amount inside the SR
Calsequestrin and sacalumenin (in longitudinal SR, facilities SERCA activity by loosely binding Ca2+).
Phospholamban, sarcolipin & myoregulin also affect SERCA activity
These generally DECREASE SERCA pump activity
PLN can be phosphorylated (PKA dependent pathway) to remove inhibition and is predominantly in cardiac, slow twitch sk mm.
278
What proteins help to sequester calcium in the SR?
SERCA ATPase
Calsequestrin
Sacalumenin - in longitudinal SR, facilitates SERCA activity by loosely binding Ca2+
279
What proteins generally decrease SERCA pump activity?
Phospholamban (PLN): can be phosphorylated (PKA dependent pathway) to remove inhibition of SERCA pump. This occurs predominantly in cardiac, slow twitch sk. muscle and works to decrease cardiac muscle rate and strength.
Sarcolipin
Myoregulin
280
Ca2+ resequestration and removal of primary importance in cardiac muscle
Na-Ca and exchanger and Ca2+ pump in the plasma membrane both extrude Ca2+ from the cell.
281
Ca2+ resequestration and removal of primary importance for skeletal muscle
Ca2+ pump sequesters Ca2+ within the sarcoplasmic reticulum (SERCA-ATPase)
Ca2+ is bound in the sarcoplasmic reticulum by calreticulin and calsequestrin.
282
Calcium binding and dissociation from actin and what occurs
When cytosolic Ca2+ rises and binds to troponin C (TrC), conformational changes cause TnT to pull tropomyosin and TnI out of the way, exposing myosin binding sites on actin so that myosin can bind to actin.
As long as Ca2+ is present, multiple cross-bridge cycles occur.
when cytosolic Ca2+ concentrations fall, Ca2+ dissociates from TpC and the subsequent movements of TnT, tropomyosin and TnI once again block further myosin-actin interactions.
283
The cross bridge cycle in muscle contraction
284
What is the force output per cross bridge?
2-5 pN - big for one cross bridge!
285
What is the importance of maintaining ATP levels in skeletal muscle fibers?
The myosin head releases the actin binding site when ATP replaces the ADP molecule. If you let ADP accumulate and let ATP diminish, ADP will remain bound to myosin and the muscle fiber won't be able to relax = RIGOR MORTIS.
Maintaining high ATP levels relative to ADP levels allows the cross bridge cycle to repeat indefinitely
286
When does cross bridge cycling stop?
Death (low ATP and buildup of ADP leading to rigor mortis)
when calcium is resequestered/dissociates from troponin C
287
Crossbridge cycle
1. Binding of ATP to the myosin head
2. The myosin head then detaches from actin
3. ATP is hydrolyzed to phosphate and ADP
4. The myosin now bound to ADP becomes weakly bound to actin
5. The binding of Ca2+ to troponin causes tropomyosin to slide over actin and enables the two myosin heads to close
6. This results in the release of of inorganic phosphate and the extension of the myosin neck leading to the power stroke of the cross bridge cycle
7. Each cross bridge exerts a force about 2 pN during the structural change
8. The release of ADP
288
How do we transmit the crossbridge force out of the sarcomere?
By using proteins like dystrophin which connect the sarcomere to the sarcolemma and out to the collagen that makes up the tendon that connect to bone.
289
Muscular dystrophy is an issue with...
dystrophin which prevents the transmission of force from the sarcomere out the to sarcolemma to tendon and then to bone.
290
Skeletal muscle fiber contraction lasts...
20-200 ms depending on the muscle fiber type
291
Sarcolemmal AP only lasts....
1-5 ms BUT it is possible to initiate another AP BEFORE twitch contraction is over
292
What is it called when another CONTRACTION (not just AP) is initiated before previous contraction has ended?
Summation
This will greatly increase force/tension development of a fiber/muscle
Tension is higher when APs occur at a higher frequency = frequency summation
This is the most energetically efficient way to increase force output/tension
293
What is tetanus and why does it happen?
When stimulation frequency is increased sufficiently so NO drop in force is seen between twitches.
This occurs when ionized Ca2+ is being released into the cytosol to create contraction
294
Which contraction is longer? Cardiac or skeletal?
Cardiac
295
What needs to occur every time there is an AP in order to have a muscle contraction?
The release of calcium from the SR into the cytosol. It doesn't matter if there is already a lot of calcium present in the cytosol - if more isn't release then there won't be a contraction
296
If the SERCA pump is inhibited, what will happen?
Muscle contraction will cease. It won't be taking ionic calcium back up into the SR to then be released again for contraction. None taken up = none released!!
297
Temporal summation
introduce another impulse before the precious contraction was finished and begin to build a larger force.
More calcium is release before the previous calcium has been sequestered
298
Tetanic state types
Unfused and fused - the force never returns to zero and all cross bridges are always engaged.
299
A non-tetanus state has a _________ appearance.
Stair step
300
What determines a single muscle twitch, temporal summation, or fused/unfused tetanus?
The amount of ionized calcium in the cytosol and how much continues to be released
301
Purpose of myoglobin
Acts as facilitative diffusion to move oxygen to the mitochondria in muscle cells. When the muscle isn't being used then it'll bind oxygen, but is mainly there to move O2 to mitochondria very quickly from sarcolemma
302
How are skeletal muscle fiber types determined?
Usually done by myosin heavy chain phenotyping
303
Myoglobin heavy chain phenotypes (3 main ones)
Type I
Type IIa
Type IIb
Others exist (type IId/x
304
Other typing nomenclature for skeletal muscle fibers (other than phenotypes I, IIa and IIb)
Twitch and oxidative characteristics
- Slow oxidative (type I)
- Fast oxidative (IIa)
- Fast glycolytic (IIb)
Both twitch and appearance (color - myoglobin content) characteristics
-Slow red (type I)
- Fast red (type IIa)
- Fast white (type IIb)
305
Postural muscles in humans are what kind of fiber type?
slow twitch/type I/oxidative
306
Relationship between conduction velocity and alpha motor neuron diameter
increased conduction velocity with increased diameter
307
Ocular muscles are what type of fiber?
IIb
308
Gastrocnemius muscles fiber type and contraction time compared to other types
Type IIa and in between I and IIb for contraction time
309
Ocular muscle fiber type and contraction time compared to other types
Type IIb and the shortest contraction time - easily fatiguable
310
Soleus muscles fiber type and contraction time compared to other types
Type I and the longest contraction time compared to the other fiber types
311
What constitutes force output? How do the different fiber types compare?
The number of cross bridges engaged.
Type I (slow) has the least force output and is fatigue resistant
Type IIa (fast, fatigue resistant) is higher than type I for force output
Type IIb (fast, fatiguable) has the highest force output. The rate of rise in this type is the fastest but is not as sustained as the other two
312
Length-tension relationship in sarcomere
Very long and very short fibers produce less force output. You want a little bit of overlap with actin and myosin but not too much and they can't be too far apart.
Short fibers: Actin starts to overlap
Long fibers: too far apart
There is an optimal length of muscle fiber/sarcomeres that will produce near maximal force.
313
Force Velocity Curve
As we lengthen the muscle, we have greater force output because dystrophin and associated proteins act as a spring connecting the contractile apparatus to the basement membrane. If you stretch the spring then you can get more force with lengthening contraction than shortening contraction
314
Types of muscle contractions (3)
Isometric
Isotonic (everything we do)
Isokinetic (doesn't occur naturally)
315
Isometric muscle contractions
NO change in muscle length, as defined by change in joint angle
Fiber lengths often change with no change in joint angle
316
Isotonic Muscle contractions
Muscle length changes against fixed load (velocity varies)
2 Types:
-Shortening (concentric)
-Lengthening (eccentric; primarily responsible for muscle injury and DOMS)
317
Isokinetic muscle contractions
Muscle length changes against fixed VELOCITY (load varies)
Also shortening and lengthening but does NOT HAPPEN NATURALLY
318
A motor unit is...
a single alpha motoneuron and ALL the muscle fibers it innervates
319
Motor unit innervation ratios
Range from 1:5-10 to 1:2000+
Those with very low ratios and found in muscles that cause precise movements such as finger muscles
Those with high innervation ratios are large muscles like leg muscles
320
Generally, fibers of a single motor unit are ...
dispersed throughout the muscle, not clustered. This aids with control of movement.
There are exceptions in cases of deinnervation and rein nervation
321
Motor unit recruitment in cases of deinnervation and reinnervation
If the motor neuron dies then the muscle nerves from adjacent muscles will reinnervate that muscle. Then single motor neuron will be innervating many muscle fibers. There will be less control in this case and occurs in polio, ALS, MS, etc.
Jerky movements
322
T/F: A muscle fiber can be innervated by many motor neurons
FALSE: a muscle fiber can only be innervated by ONE motor neuron
323
Large motor neurons typically innervate type _____ fibers and have ____ innervation ratios. These are designed for _____ output and very _____ durations.
IIb
high
maximal
short
Explosive movements with short duration recruit by IIb fibers from large motor neurons that recruit many muscle fibers
324
Types of motor units and what they are based on
Based on n'conduction velocity and fatigue resistance during isometric contraction
-FR (fast, fatigue resistant) Type I
- FF (fast, fatiguable) Type IIb
-FI (fatigue intermediate, fatigue resistant) Type IIa
Correlates with number of fibers innervated
Also correlates with fiber twitch mechanics, oxidative capacity
325
Spatial summation
Also called multiple fiber summation
Mechanism by which whole muscle can develop relatively constant force over time
Achieved by activating individual MOTOR UNITS asynchronously
-More efficient that bringing fewer motor units to tetanus
-Allows for most control over force output
-ESSENTIAL FOR FINE MOTOR CONTROL involving low innervation ratios
326
What is the most important way for skeletal muscle to resequestrate calcium?
SERCA pump (L-type calcium channel that is inhibited by phospholamban - this is more important in cardiac muscle).
The SERCA pump is also important in cardiac muscle, but since skeletal muscled doesn't have the membrane ion exchanger pumps that cardiac muscle does, it relies on SERCA pumps to get calcium out of the cytoplasm
327
Membrane ion exchanger pumps are more important in _____ muscle than they are in _____ muscle.
Cardiac
Skeletal
328
Myosin releases from the actin binding site when...
ATP replaces the ADP molecule on the myosin head
329
