Week 2- Nerve and Muscle Physiology Flashcards
1
Q
Diffusion potential
A
A potential difference generated across a membrane by ions flowing down their concentration gradient
2
Q
Role of permeability in creating diffusion potential
A
The membrane has to be permeable to that ion
3
Q
What determines the size of the diffusion potential?
A
The size of the concentration gradient
4
Q
Equilibrium potential
A
- A diffusion potential
- The potential difference across the membrane when ions have reached equilibrium (no net diffusion)
- Chemical and electric driving forces are equal and opposite
5
Q
What equation calculates the equilibrium potential
A
Nernst equation
6
Q
Potassium accumulates where?
A
Inside the cell
7
Q
Sodium accumulates where?
A
Outside the cell
8
Q
Membrane potential
A
Difference in electrical charge across a membrane
9
Q
What can cause the membrane potential?
A
- Passive ion diffusion (ex: open Na+ channel)
- Electrogenic pumping (ex: Na+/K+ ATPase)
10
Q
Is the cell membrane more permeable to Na+ or K+
A
AT REST, K+; there are K+ leak channels
11
Q
How is equilibrium different than having the same chemical concentration?
A
Equilibrium takes into account the electrical charges present and their effects on flow as well as the chemical concentration of ions
12
Q
Why is resting membrane potential (Vm) so close to E(K)?
A
The membrane is more permeable to K+ than to Na+
13
Q
Why is the cell membrane more permeable to K+ than Na+
A
- Na+/K+ pump
- K+ leak channels
14
Q
What would a saline solution of KCl do to membrane potential?
A
It takes away the membrane potential, and when this happens to the heart or diaphragm, no action potential can take place, killing the person.
15
Q
Depolarization
A
Potential becomes less negative
16
Q
Hyperpolarizationn
A
Potential becomes more negative than resting membrane potential
17
Q
Overshoot
A
More positive than 0 mV
18
Q
Repolarization
A
Potential moves toward resting membrane potential (more negative)
19
Q
Excitability
A
The potential can change from resting membrane potential, can depolarize and repolarize
20
Q
Threshold
A
The potential at which an action potential will always happen
21
Q
Action potential
A
Regenerating depolarization that propagates along an excitable membrane
22
Q
Propagate
A
Conducts without getting weaker
23
Q
Excitable
A
Capable of generating an action potential
24
Q
How fast are action potentials?
A
~60 m/s
25
Basic characteristics of an action potential
- All-or-nothing
- Constant amplitude
- Starts w/ depolarization
- Involves change in permeability
- Relies on voltage-gated channels
- Constant conduction velocity
26
All-or-nothing
Action potential will not happen unless depolarization reaches a threshold voltage (~15 mV positive to resting)
27
Constant amplitude
- APs are not additive
| - Info depends on frequency
28
Starts w/ depolarization
Requires a stimulus for depolarization
29
Involves change in permeability
Na+ flows into the cell
30
Relies on voltage-gated channels
Determines which ions can come in and out of the cell
31
Constant conduction velocity
- True for any given fiber, but not across all fibers
| - Larger diameter => faster
32
Velocity for myelinated fibers
V (m/s) = fiber diameter (mm) x 4.5
33
Velocity for unmyelinated fibers
V (m/s) = square root of fiber diameter
34
At rest, which gates are open for Na+ voltage gated channels?
- Activation gate = closed
| - Inactivation gate = open
35
What happens to the Na+ activation gates after action potential occurs?
- Activation gate opens
| - Same stimulus closes inactivation gate, but this happens more slowly
36
What happens to the K+ activation gates after action potential occurs?
- Starts closed
| - Opens slowly
37
What happens during the upstroke of the action potential?
- Na+ permeability increases
| - Happens because Na+ channels open
38
What happens during the downstroke of the action potential?
- Na+ permeability decreases
| - K+ permeability increases (K+ channels open)
39
How do nerves prevent action potentials from propagating backwards?
Inactivation gates and refractory periods
40
Myelinationn
Axons are surrounded by a myelin sheath
41
What cells are responsible for myelination?
Schwann cells
42
Node of Ranvier
A break in the myelin occurring every 1-3 mm
43
Saltatory Conduction
Current travels faster under the myelin, and is amplified at the nodes of Ranvier
44
Multiple sclerosis
Auto-immune disease where in nerves of the CNS demyelinate
45
Main classes of muscle cells
- Skeletal muscle
- Cardiac muscle
- Smooth muscle
- Myoepithelial cells
46
Muscle organizational hierarchy
Muscle --> Fasciculus --> Fibers --> Myofibrils --> Sarcomeres --> Myofilaments
47
Epimysium
Connective tissue that surrounds the entire muscle
48
Perimysium
Connective tissue that surrounds each fasciculus
49
Endomysium
Connective tissue that surrounds each muscle fiber
50
Where are blood vessels and nerves that supply muscles located?
In the perimysium
51
Sarcomere
Portion of the myofibril between 2 adjacent Z disks
52
Light Bands
- I band
| - Only actin
53
Dark Bands
- A band
| - Actin and myosin overlapping
54
Where is actin found outside of the muscle?
- Cytoskeleton of the cell
- Determines shape of the cell's surface
- Important for whole cell locomotion
55
Alpha-actinin
- Contractile bundle
| - Loose packing allows myosin-II to enter the bundle, permitting contraction
56
Fimbrin
- Parallel bundle
| - Tight packing prevents myosin-II from entering the bundle, making contraction impossible
57
Myosin-II
- Part of a superfamily of myosin proteins
- Myosin superfamily is part of a larger family of motor proteins
- Skeletal muscle myosin was the first motor protein identified
58
If myosin-II was the first motor protein identified, why is it called "myosin-II"?
It has two heads
59
Composition of myosin
- 2 heavy chains (in the tail)
| - 4 light chains (part of the head)
60
How many individual myosin molecules make up the myosin myofilament?
200+
61
What are the protruding heads of myosin called?
Cross-bridges
62
Titin
Spring-like protein that connects myosin with z-line
63
Troponin
Binding site for calcium in skeletal muscle
64
Tropomyosin
- Wraps around actin
| - Stabilizes the thin filament
65
Tropomodulin
Caps actin closer to the M line
66
Cap Z
Caps actin at the Z disc in conjunction with alpha-actinin
67
Does the length of the muscle filaments change during muscle contraction?
No
68
How often does the myosin head cycle during a muscle contraction?
~5x/second
69
Nebulin
- Molecular ruler
| - Helps determine the exact length of each actin filament
70
Steps of the Walk-Along Theory of Contraction
- Attached
- Released
- Cocked
- Force-generating
- Attached
71
Attached
- Start of the cycle
- Myosin head is attached to actin
- ATP absent
- Short-lived phase during active contraction
72
Released
- ATP binds to myosin head
| - This allows myosin to detach from actin
73
Cocked
- Head moves along the actin filament
| - ATP hydrolysis, ADP and P(i) stay bound to myosin head
74
Force-generating
- Weak binding causes release of P(i)
- Tight binding occurs at the same time
- POWER STROKE
- ADP is lost during power stroke, returning to start of cycle
75
Parts of troponin complex
- Troponin I
- Troponin C
- Troponin T
76
Troponin I
Inhibits binding of myosin head
77
Troponin C
- Binds to calcium
| - Causes tropomyosin to move out of the way, making room for myosin heads
78
Troponin T
Binds to tropomyosin
79
Types of synapses
- Electrical
| - Chemical
80
Electric Synapse
Allows current to flow from one excitable cell to another via gap junctions
81
How high is resistance in gap junctions?
Low
82
Where are electrical synapses found?
Cardiac muscle and some types of smooth muscles
83
Directionality of electric synapses
Bidirectional
84
Synaptic delay in electric synapses?
No synaptic delay
85
Chemical Synapse
There is a gap b/t the presynaptic membrane and post synaptic membrane
86
What is the gap between the pre- and postsynaptic membrane called?
synaptic cleft
87
How is information transmitted b/t the pre- and postsynaptic cleft?
Via neurotransmitters
88
What two effects can the potential have in a chemical synapse?
- Excitatory
| - Inhibitory
89
Directionality of chemical synapses
Unidirectional
90
Synaptic delay in chemical synapses?
There is a synaptic delay
91
Neuromuscular Junction
Connection b/t nerve and muscle fiber
92
Motor End Plate
Part of the muscle fiber in direct contact with the nerve
93
Why are there invaginations in the motor end plate?
To increase surface area for neurotransmitters to diffuse
94
What are the receptors for ACh called?
Nicotinic receptors
95
What happens when ACh binds to the receptor?
Na+ flows into the cell
96
Why do only Na+ ions pass through, when the nicotinic channel is big enough for K+ and Ca2+ as well?
- Only Na+ and K+ have large enough concentration
| - Negative potential attracts Na+ influx and prevent K+ efflux
97
End-plate potential
- The local positive potential that occurs when ACh binds to the nicotinic receptor
- Generates action potential
98
How much can the potential change in the end-plate potential?
50-75 mV
99
How much potential change is required for an action potential?
20-30 mV
100
What causes the stimulation of the motor end plate to end?
Removal of ACh
101
How is ACh removed?
- ACh-esterase enzyme
| - Spillover of ACh
102
What is ACh spillover?
Some ACh will diffuse out of the synaptic cleft into the interstitial space
103
What enzyme facilitates the formation of ACh?
- Choline acetyltransferase
| - Choline + Acetyl CoA -- "ase" --> ACh
104
What is the reaction for ACh degradation?
ACh -- "ase" --> Choline + Acetate
105
Steps of the Neuromuscular Junction
1) Nerve impulse arrives, opens voltage-gated Ca2+ channels --> stimulates release of ACh
2) ACh binds to nicotinic receptors on muscle cell, allowing the ACh-gated channel to open, bringing in Na+ (End-plate potential)
3) Influx of Na+ causes local depolarization, opening Na+ voltage-gated channels, causing the action potential
4) Impulse reaches T-tubules, causes dihydropyridine (DHP) receptor to open
5) DHP opening causes the Ca2+ release channel (ryanodine receptor) on SR to open and release Ca2+ --> cross-bridge cycle
106
How is calcium put back into sarcoplasmic reticulum
SERCA
107
Excitation-Contraction Coupling
Action potential --> myoplasmic [Ca++] goes up --> muscle twitch
108
Steps of Excitation-Contraction in skeletal muscle
1) AP in muscle membrane
2a) Depolarization of T-tubules
2b) SR opens and releases Ca++ (DHPR pulls open ryanodine receptors)
3) Intracellular [Ca++] goes up
4) Ca++ binds to tropinin-C
5) Tropomyosin moves, allowing actin and myosin to interact
6) Cross-bridge cycling
7) Ca++ collected by SERCA into SR --> relaxation
109
Agents that alter neuromuscular function
- Botulinum toxin
- Curare
- Tetrodotoxin
- Neostigmine
- Hemicholinium
110
Botulinum toxin
- Blocks ACh release from nerve terminal
| - Causes paralysis and eventually death (respiratory failure)
111
Curare
- Competes w/ ACh for its receptor
- Max doses cause paralysis and death
- Therapeutically used for anesthesia
112
Tetrodotoxin
- Japanese puffer fish
| - Inhibits Na+ channels
113
Neostigmine
- AChE inhibitor
| - Used to treat Myasthania Gravis
114
Hemicholinium
Blocks choline reuptake, depleting ACh stores
115
Excitatory Postsynaptic Potential
Depolarizes the postsynaptic cell
116
Examples of EPSPs
- ACh
- Norepinephrine
- Epinephrine
- Dopamine
- Glutamate
- Serotonin
117
Inhibitory Postsynaptic Potential
- Hyperpolarize postsynaptic cell
| - Via opening Cl- or K+ channels
118
Examples of IPSPs
- GABA
| - Glycine
119
Length-Tension Relationship
- There is an ideal level of overlap between actin and myosin to maximize tension
- Too much or too little overlap will lead to less tension
120
What produces passive tension?
The cytoskeleton and other connective tissue
121
When does passive tension come into play?
Only at longer lengths
122
What is the force-velocity relationship?
- As force goes up, velocity goes down
| - As force goes down, velocity goes up
123
How is speed of contraction determined?
Vmax of myosin ATPase
124
Characteristics of high Vmax of myosin ATPase
- Stained white
- Rapid cross-bridge cycling
- Rapid rate of shortening (fast fiber)
125
Characteristics of low Vmax of myosin ATPase
- Stained red
- Slow cross-bridge cycling
- Slow rate of shortening (slow fiber)
126
Fast vs slow twitch fibers in whole muscle
Most muscle have both types, with differing proportions
127
Fiber types and motor units
All of the fibers in a given motor unit will be the same fiber type (i.e. fast or slow)
128
Characteristics of Slow (Type I) fibers
- Oxidative
- Small diameter
- High myoglobin content
- High capillary density
- Many mitochondria
- Low glycolytic enzyme content
129
Characteristics of Fast (Type II) fibers
- Glycolytic
- Large diameter
- Low myoglobin content
- Low capillary density
- Few mitochondria
- High glycolytic enzyme content
130
How many fibers are in small motor units?
As few as 10 fibers/unit
131
Function of small motor units
- Precise control
| - Rapid reacting
132
How many fibers are in large motor units?
As many as 1000 fibers/unit
133
Function of large motor units
- Coarse control
| - Slower reacting
134
Why do motor units overlap?
Provides coordination
135
Size principle
Motor units will be recruiting from smallest to largest
136
Force summation
Increased contraction intensity as a result of the additive effect of twitch contractions
137
Types of force summation
- Multiple fiber
| - Frequency
138
Multiple fiber summation
- Increase in number of motor units contracting at the same time
- Size principle
139
Frequency summation
Increase in the frequency of contraction in a single motor unit
140
Staircase Effect
- Decreasing [Ca++] initiates relaxation
- If the muscle is stimulated before relaxation completes, the new twitch adds onto the previous one
- If AP frequency is high enough, the twitches add together until "fused tetanus"
141
Ways muscles remodel and grow
- Hypertrophy
- Hyperplasia
- Lengthening
142
Muscle Hypertrophy
- Common
- Takes weeks
- Caused by near maximal force development
- Myofibrils split
- Increased force generation
143
Muscle Hyperplasia
- Rare
- Formation of new muscle fibers
- Can be caused by endurance training
- Increased force generation
144
Muscle Lengthening
- Occurs with normal growth
- No change in force development
- Greater shortening capacity and speed of contraction
145
Muscle Atrophy
- Shrinking of muscle fibers
| - Weeks/months
146
Muscle Atrophy w/ fiber loss
- Muscle fibers shrink to the point of disappearing
- Disuse for months/1-2 years
- Very difficult to replace lost fibers
147
Causes of atrophy
- Devervation/neuropathy
- Tenotomy
- Sedentary lifestyle
- Plaster cast
- Space flight (zero gravity)
148
Effects of atrophy on muscle performance
- Degeneration of contractile proteins
| - Decrease max force and velocity of contraction
149
Why does smooth muscle lack striations
- Striations come from actin and myosin arranged in sarcomeres
- Actin and myosin are not arranged in sarcomeres in smooth muscle
150
Smooth muscle functions
- Motility
| - Tension
151
Smooth muscle and motility
- Move things through passages
| - EX: propel chyme through GI tract
152
Smooth muscle and tension
EX: maintain appropriate vascular diameter in blood vessels
153
Types of smooth muscle
- Unitary/Visceral/Single-unit
- Multiunit
- Combo
154
How are unitary/visceral/single-unit smooth muscle cells connected?
Via gap junctions
155
Where are unitary/visceral/single-unit smooth muscles located?
- GI tract
- Bladder
- Uterus
- Ureter
156
Characteristics of Unitary/Visceral/Single-unit
- Spontaneous pacemaker activity (slow waves)
| - Mostly phasic
157
How are multiunit smooth muscles connected?
NOT by gap junctions
158
Where are multiunit smooth muscles located?
- Iris
- Ciliary muscles of the lens
- Vas deferens
159
Characteristics of multiunit smooth muscles
- Each fiber acts as its own unit
- Little/no coupling between cells
- Densely innervated by ANS
- Mostly tonic
160
Where is combo smooth muscle located?
Vascular smooth muscle
161
How does smooth muscle differ from skeletal muscle?
- Has actin and myosin, but no troponin complex
| - No striations
162
Dense bodies in smooth muscle
- Serve similar function to Z discs
| - Large numbers of actin attached to dense bodies
163
How much can smooth muscle contract vs skeletal muscle?
Up to 80% of their length vs 30% in skeletal muscle
164
Myosin ATPase activity in smooth muscle compared to skeletal muscle
- Very reduced
| - 1/10 to 1/300 the amount of energy to maintain the same tension
165
Time for contracting and relaxing in smooth muscle vs skeletal muscle
Smooth muscle needs more time to contract and relax
166
Maximum force in smooth vs skeletal muscle
- 4-6 kg/cm^2 in smooth muscle
| - 3-4 kg/cm^2 in skeletal muscle
167
How does smooth muscle maintain tonic contractions for long periods of time?
Uses minimal energy using the latch mechanism
168
Stress relaxation vs reverse stress relaxation in smooth muscle
Increases or decreases tension to maintain pressure to accommodate large changes in volume (i.e. blood pressure)
169
Myogenic
- Spontaneously active
| - Smooth muscle is myogenic
170
State of the SR in smooth muscle
Poorly developed
171
How does excitation-contraction coupling differ in smooth vs skeletal muscle?
- Same actin-myosin interaction
| - No troponin complex
172
When does myosin hydrolyze ATP in smooth muscle?
When myosin is phosphorylated on the regulatory light chain
173
Myosin light chain kinase
- MLCK
| - Phosphorylates the light chain (attaches a phosphate)
174
Myosin light chain phosphatease
- MLCP
| - Removes a phosphate
175
How is smooth muscle myosin-based?
Skeletal muscle is regulated through actin, but smooth muscle is regulated through myosin
176
How is smooth muscle Ca++ sensitive?
MLCK is active only when Ca++ is bound to calmodulin
177
Major points of smooth muscle contraction
1) "Stimulus" causes Ca++ to enter the cell (either from ECF or SR)
2) Ca++ binds to calmodulin
3) Ca++/calmodulin/MLCK complex leads to phosphorylation of myosin light chain (requires 1 ATP)
4) MLC is part of the myosin head
5) Phosphorylated myosin head binds to actin leading straight into power stroke (automatic)
6) 2nd ATP is required to release myosin head from actin
7) Cross-bridge cycling requires both MLCK and MLCP
8) MLCP activity can change calcium sensitivity
178
What can stimulate skeletal muscle vs smooth muscle?
```
Skeletal Muscle
- Nervous system
Smooth Muscle
- Nervous system
- Hormones
- Stretch
- Other chemicals
```
179
Complexity of smooth muscle neuromuscular junction vs skeletal muscle
Less complex and less understood than skeletal muscle
180
Varicosities
Bulges terminal axons that contain neurotransmitters
