Exam 2 Flashcards
Permeability of the membrane before, during, and after an AP
Before, K+ is much greater
During, Na is much greater
After, K+ is high once again
What keeps the membrane potential near Ek at rest
Leaky K+ channels
Long QT syndrome
Takes longer to repolarize after the action potential
Glucose-sodium cotransporter
Two sodium for every glucose molecule, can get 10,000 fold conc. gradient for glucose
Most important countertransporter in the body and why
Na/H exchanger, cell pH is basic because protons are constantly pumped out using sodium
Digitalis (oubain)
inhibits the Na/K ATPase, causing reverse operation of the Na/Ca exchanger, raising cytoplasmic Ca2 and producing a more powerful heart contraction
Voltage sensor
Polar element within a membrane that moves to one side or another based on charge
3 regions of a pore module
Selectivity filter, cavity, and gating
Are there synapses in sensory ganglia
No
Afferent vs. efferent
Afferent (towards a source), sensory
Efferent (away from a source), motor
Where are pseudounipolar neurons found
Exclusively in sensory ganglia in the PNS, single short process bifurcates into two other processes
Axon hillock and rough ER
It has no Nissl substance
MAP’s
Microtubules-associated proteins that compartmentalize the neuron
What part of a neuron is lost with age
Dendritic spines
Anterograde neuronal transport
Kinesis, 400 mm a day
There is also slow, diffusive transport (enzymes and neurotransmitter precursors)
Neurofibrillary tangles
Caused by tau protein that causes crosslinking of microtubules in alzheimers, down’s etc.
Retrograde axonal transport
Mediated by dynein, recycles substances, can take up toxins and viruses
Oligodendrocyte
Makes CNS myelin, multiple axons
Microglia
CNS macrophage, smallest cell, derived from monocytes
Proliferate to site of CNS injury, determine survival of a tissue graft
Astrocytes
Ensheath the synapse, store glycogen
Foot processes make the blood-brain barrier
Most common glial cells in the CNS
Proliferate to injuries and form an astroglial scar
Are similar to neurons but are not polarized
GFAP
Glial Fibrillary Acidic Protein, expresses by astrocytes
Ependymal cells and tanycytes
Other two glial CNS cells
Satellite cells
Microenvironment around a ganglion, pathway for metabolic exchange
Schwann cells
Make all PNS myelin
Guillane-Barre syndrome vs. MS
MS is CNS myelin disorder, Guillane barre is PNS myelin
What myelin proteins cause compaction of schwann cell myelin
P0 and MBP (Myelin Basic Protein)
Are nodes of ranvier larger in the CNS or the PNS
Larger in the CNS, making saltatory conduction more efficient
Neuregulin
Signal that causes myelination, derived from axon size
Wallerian degeneration
Anterograde degeneration, axon degenerates distal to the cut, cell body undergoes retrograde chromatolysis
Molecules that cause lack of CNS regrowth
Nogo, MAG, and OMgp
Epineurium
Connective tissue around surface of entire nerve
Perineurium
Blood nerve barrier, surrounds each fascicle of nerve fibers
Endoneurium
Surrounds each nerve cell and is made of collagen and reticular tissue
Cystic Fibrosis
Mutation in CFTR, mucus in lungs cannot trap bacteria
ASL
Airway surface liquid, below the sticky mucus that cilia beat out of the lungs, 8 microns high
Passage of CL from lumen of the lungs
Can be paracellular or transcellular, follows sodium, net effect is a pumping of NaCl from the apical to the basolateral membrane, and water follows, dehydrating the ASL
CF heterozygote advantage
May mae you more resistant to cholera-induced diarrhea
Cholera mechanism
Activates the CFTR regulatory domain, ion channel always opened and dehygration occurs
Cholera and glucose treatment
Sodium glucose transporter causes water to obligatorily come with the glucose, counteracting the loss in the cholera
What can the reflex arc at the patellar tendon be used to detect
pre-eclampsia
Why does AP depolarization not go backwards
Sodium channels remain inactivated (cannot reopen) and the voltage gated potassium channels are slow to close
Myelin and capacitance
Myelin decreases the effective membrane capacitance
how does a chemical synapse work
Depolarization opens voltage gated calcium channels
Ca ions bind to SNARE proteins, vesicles fused with the membrane and Ach is released
Botulin toxin
Blocks the vesicle fusion process by cleaving SNARE proteins that are required
High Safety Factor
Endplate potential brinds the membrane potential to the AP threshold every time
How many nuclei do smooth muscle have
1
Electrical isolation properties of the different muscle cells
Skeletal muscles are isolated electrically, cardiac and smooth muscles are connected to neighboring cells (smooth can sometimes be isolated)
Satellite Muscle Cells
Closely associated with muscle fibers, can be reactivated at any time, re-enter the cell cycle, and generate new cells to fuse into
Tend to have totallly condense chromatin
When are the nuclei of muscle cells centrally located
When the fiber is damaged
A band
The extent of the thick myosin filaments
H band
Parts of the myosin band where there is no actin present
I band
Parts where only actin is present
M line
Narrow dark line in the center of the A band, L line is the narrow light line next to the M line on each side
Z band
High density of protein on the edge of each sarcomere
Myomesin
Proteins in the M band that bind the thick myosin filaments together
Myosin II
The myosin that is found in muscle, made up of 2 essential light chains, 2 regulatory light chains, and 2 heavy chains
In what part of myosin does phosphorylation occur
At the end motor domains, on the regulatory lgith chains
Actin and Myosin and polarization
The actin filament is polarized, unlike the myosin filament.
the pointed end of actin is the minus end, while the barbed end is the plus end
Tropomodulin
Capping protein that regulates acin polymerization and depolymerization at the pointed end of the actin filament
CapZ
Capping protein that regulates actin polymerization and depolymerization at the barbed end
Titin
Elastic protein that forms connections between Z discs and myosin filaments
Myosin and actin in the absence of ATP
Bind tightly, rigor mortis
When does the power stroke occur
As phosphate is released. When ADP dissociates, myosin minds to actin again
Tetanus
Completely fused twitches
Also a bacteria - cleaves synaptobrevin which blocks the release of inhibitory NT’s, permitting unopposed neural stimulation
Positive After Potential
Occurs in skeletal muscle, AP in the T-tubular membranes takes place slightly after that on the surface membrane
Sarcolemma
Depolarization of the plasmalemma, results int he release of calcium from the SR
SR
Located in the space between the myofibrils of the muscles, enabling a simultaneous release of Ca2
T tubules
Invagination of the surface membrane that penetrate into muscle and form a transverse network at 1-2 sacromeric intervals
They depolariz when the surface of the muscle fiber depolarizes
Triad
T-tubule sandwiched between two SR membranes
Feet
Small densities that span the SR and T tubule gap and connect one membrane to the other
What occurs when the foot gate of the triad opens
Ca moves from the SR lumen into the myoplasm
Where is calcium for contraction stored in skletal and cardiac muscle
Skeletal - SR
Cardia - extra cellular fluid
How does calcium removal occur following contraction
Na-Ca exchanger and the Ca (ATPase) pump (this pump sequesters Ca within the SR)
State of muscle relaxation
Regulatory proteins inhibit actin-myosin interactions, and the sarcomere can be stretched passively
Ca and troponin
Ca binds to the troponin C portion of the troponin complex, which loosens tropomyosin, uncovering actin molecules so that they can interact with myosin heads
Motor unit
Single motoneuron innervates multiple muscle fibers
What is force production (micro-level) dependent on
The number of sites on which crossbridges can form (between actin and myosin)
What is total tension in a muscle determined by
Sum of active (actin and myosin) and passive (elastic, such as titin) tension
How can passive tension be calculated
Do an experiment in the presence of ATP but in the absence of calcium
ADP release and velocity
Quicker ADP release, faster velocity
Advantage and disadvantage of long muscle fibers
Length tension curve is spread out, but it increases the amount of ATP used
Isometric contraction vs isotonic
Muscle develops force at a constant length (metric)
shortens under constant load (tonic)
Slow vs. fast muscle fibers
Slow are red muscle, darker, fatigue resistant, low ATPase, use oxidation
Fast aare paler, easily fatigued, high myosin and glycogen, some can also be red
Red fibers
Many mitochondria, can maintain loads over long periods of time, have more capillaries and increased generation of ATP
Myasthenia gravis
Ptosis, fatiguability of muscles
Failure of endplate potentials
AP potential latency increases with each stimualatin, and at a certain point the EPP does not hit the threshold voltage
The safety factor is small, failure in neurotransmission
MEPP
Miniature Endplate Potential, caused by the release of one Ach vesicle
Ach and Myasthenia gravis
The number of ACh receptors is about 33% of normal, less junctional folding as well, synaptic cleft is wider
Antibodies and MG patients
Myasthenia Gravis humans have antbodies to the ACh receptor, inducing clumping for degredation
How is MG managed
AChesterase inhibitors
(prostigmin and mestinon)
Henneman’s Size Principle
The smaller the motor neuron, the smaller the number of muscle fibers it innervates
This allows for the gradation of force, percentage increase is constant
Optical trap experiment
Showed that a fast skeletal myosin spends much longer in the detatched state that smooth muscle (smooth holds force longer)
Determined by the rate of ADP release
Slow nerve innervating a fast twitch muscle (splicing experiment)
Causes the muscle to become slow
Dystrophin
Transfers force between muscle fibers through adhesions
Myostatin
Negative regulator of muscle growth, lack of this causes uninhibited muscle growth
Smooth muscle and modulatory proteins
Caldesmon and calponin have the modulatory functionality (no troponin), tropomyosin still exists
Ratio of actin in skeletal vs. smooth muscle
There is twice as much actin, more variable myosin bonding, no 1:1 correspondence with actin
What regulates contraction in smooth muscle
Calcium binds to calmodulin, myosin must be phosphorylated to be active
Dense bodies
Cytoplasmic connections in smooth muscle (connected by desmin, an intermediate filament)
MLCK
Myosin Light Chain Kinase, regulated by Ca, activates smooth muscle myosin on the regulatory right chain
At low Ca, it is inactive, When it is active, it phosphorylates myosin and enables it to interact with actin
Smooth muscle and t-tubules
There are no T tubules in smooth muscle, only Sarcoplasmic Reticulum
Maximum myosin binding and output
Only around 60% of myosins in a cell need to be phosphorylated to reach maximum output
Restoring force in smooth muscle
Intermediate filaments that have been compressed
Nitric Oxide in smooth muscle
Activates the phosphatase and relaxes smooth muscle
Force-Velocity curve in smooth muscle
Hyperbolic
Single unit, phasic smooth muscle
Rapid contraction and innervated by one neuron
Multiunit, tonic smooth muscle
Vascular, holds the position, slow contraction, one neuron innervates many
Funny currents (If)
At the end of cardiac muscle repolarization, ion channels that conduct slow, depolarizing NA currents open
Junctions between cardiac myocytes
Gap junctions and intercalated discs
What are refractory periods due to
Fraction of potassium channels that remain open
How is calcium removed from the cytoplasm in cardiac muscle
Na-Ca exchanger, and the SERCA pump
Starling’s Law of the Heart
Whatever the heart receives, it will find a way to output
If the muscle is stretched out, contraction is stronger at longer lengths
Skeletal muscle vs. cardiac muscle vs. point in contraction
In skeletal muscle, it is weakest at the beginning or end of a motion
In cardiac muscle, there is no descending limb in the length-tension relationship
Things that cause Starling’s law to be true
Length dependence of Ca sensitivity - as sarcomere length is increased, the amount of force you get for the same degree of calclium also goes up
What is the most important determinant of afterload in the heart
Diastolic blood pressure
Force-Frequency response of the heart
Faster heart rate increases cardiac output, not just pressure
In heart fairue, there is a negative force-frequency response
Ratio of SERCA and NCX
If SERCA is greater, there is increased contractility when Ca goes up
If NCX is greater, there is decreased contractility when Ca goes up
Inotropy
The ability of heart muscle to develop force at a fixed length
How is force regulated in skeletal vs. cardiac muscle
In skeletal - # of motor units activated
In cardiac - regulated by cytosolic Ca and Ca sensitivity
Ca sensitivity is regulated by sarcomere length and phosphorylation of sarcomeric proteins
Phases of the cardiac action potential
0 - upstroke of the AP, sodium channels
1 - initial rapid repolarization (small)
2 - plateau, slow repolarization
3 - steep slope downstroke
4 - resting potential
Activation and inactivation gates of the cardiac sodium channel
Only a small frame where they are both open based on voltage, but both gates are open for a short time because inactivation is slower than activation
Rectifier currents
Restore the polarization, have bent slopes
How does High K+ concentration affect action potentials
If the membrane starts off at a higher potential, fewer inactivation channels are available to open and then close, so action potentials will be smaller
T-Type Ca Channel
Inactivate quickly, transient
L-type Ca channel
Much slower than Na channels, longer lasting
All important channels over time during a heartbeat
Sodium, LCa and TCa open, depolarizing
T type close at the end of phase 1, ending the partial repolarization
L type calciu channels slowly close and delayed rectifier K channels open during the plateau
Plateau drops sharply when the K1 inward rectifier opens
Action potentials of the different chambers of the heart
Ventricular AP is slightly longer than the atrial AP
SA node has slow upstrok and slow repolarization
Purkinje fiber has a sharp immediate spike, and the plateau is at a more negative membrane potential
What is the order of AP’s in different places in the heart
SA, Atrium, AV, Bundle of His, Purkinje, Ventricle
Pacemaker current
If
P-wave
QRS Complex
T-wave
P wave is excitation over the atria
QRS complex is flow of excitation over the ventricles
T-wave is flow of repolarization in the ventricles
What is a DHPR
A calcium channel in the triad that moves from the T-tububle to the SR membrane
Differences between Cardiac and Skeletal Muscle E-C Coupling
A big portion of calcium in cardiac muscle comes from the extracellular space
Cardiac AP is much longer
In heart, Ca entry causes Ca release from the SR, while in skeletal muscle direct action between the DHPR transporter and RyR causes the Ca2 release
Three alterations to pacemaking cells that change heart rate
Reduced rate of phase 4 depolarization
Less negative threshold
More Negative max diastolic potential
Parasympathetic Action on the SA Node
Ach from the vagus nerve decreases heart rate by increasing K+ Permeability
K-ACh potassium channel is what is affected
Three alterations in strength of cardiac contraction
Increased Ca
More Sensitive to Ca
More Force at each concentration of Ca
Rate straircase
If the heart rate increases, strength of contraction becomes higher
Mechanism of the Rate Staircase
Contraction strength increases at high rates because diastole shortens more than systole, this leads to a higher proportion of the cardiac cycle in systole at a higher rate
Balance between influx and efflux changes
Not as much time to pump the calcium back out - calcium stays in to cause a stronger beat
Catecholamines (sympathetic action) and the heart
Increase strength of contraciton by increasing Cyclic AMP which increases calcium pumping by the SR, even though there is a decreased sensitivity to calcium
However, overall there is an increased force
What cell specialization allows calcium to be released simulataneously around a muscle
T-tubules
Where can alpha-actinin be found
In the Z band, at the beginning and end of each sarcomere
Dorsal root ganglion and synapses
No synapses occur in that space
What is the difference between unmyelinated nerves in the CNS vs. those in the PNS
Those in the PNS are still enveloped by cytoplasmic processes of a Schwann cell. These cells act as phagocytes and remove neuronal debris in the PNS after injury. In the CNS, they are bare and not ensheathed by oligodendrocytes
Cholinergic transmission
All preganglionic autonomic neurons
All parasympathetic postganglionic neurons
Sweat gland and blood vessel sympathetic postganglionic neurons
Adrenergic postganglionic neurons
Norepinephrine, noradrenaline
All other sympathetic postganglionic neurons
How is norepinephrine removed from the synapse
Direct sodium driven reuptake into the nerve terminals
What is the Ach receptor in the somatic NS
Nicotinic receptor N1
What is the ach receptor in the postganglionic neuron and terminal receptor in parasympathetic innervation
N2 Ach receptor in the postganglionic, muscarinic receptor in the target
What is the Ach receptor in the sympathetic postganglionic neuron and target
N2 receptor in postganglionic, Adrenergic norepinephrine receptor in the target organ
Except for nicotinic Ach receptor, how do autonomic receptors exert their effects
Membrane-bound G proteins
Nicotinic vs. Muscarinic Ach receptors -
Nicotinic are excitatory, M receptors stimulate second messengers that have varying effects
B1 receptors are found where
In the heart
B2 receptors are found where
Bronchiole relaxation, inhibitory
A1 and A2 receptors
These are epinephrine or norepinephrine receptors, a1 is excitatory and a2 is inhibitory
DHPR
The voltage sensor in T-tubules that changes shape with depolarization ona results in conformational changes of the ryanodine receptor in the SR that opens the gated Ca release channels
Transverse and longitudinal components of the intercalated disc of cardiac myocytes
Transverse: fascia adherens, macula adherens
Lateral - gap junction, providing ionic continuity
EC coupling differences between skeletal and cardiac muscle
In cardiac muscle, the Ca channels and voltage sensory interact indirectly via calcium ions with the ca release channels of the SR
What are the astrocytes in white vs. gray matter called
Protoplasmic astrocytes (gray)
Fibrous astrocytes (white)
What morphologic type of neuron is found in dorsal root ganglia
Pseudounipolar neurons
How can you distinguish a dorsal root ganglion cell from an autonomic ganglion cell
Autonomic ganglion cells have an eccentric nucleus and are only partially surrounded by satellite cells
DRG cells have no synapses and a central nucleus, and are completely surrounded by satellite cells
What contains the L-type receptors
T-tubules
What does cAMP do to the heart
Increases contractility by increasing calcium, increasing the force of contraction
It also increases Ca reuptake by the SR, leading to an increased rate of relaxation
What role does calmodulin play in smooth muscle contraction
Calcium binds to calmodulin which then activates MLCK, Which then phosphorylates the myosin light chain
In the airway, what is the pathway for transepithelial Cl movement
The paracellular pathway, the Cl moves through the tight junctions
