LEC18: Membrane Excitability

Question 1

what kind of channels are in membrane that exhibits passive membrane behavior?

what does this mean?

Answer 1

current flow across membrane of only voltage-independent “leak” channels

resulting voltage change: as predicted by Ohm’s law, w/ delay b/c of capacitance

V_m returns directly to original value when current ends

Question 2

what kind of channels are in membranes that show active properties?

Answer 2

membranes including voltage-dependent channels - conductances respond to changes in V_m, which is reflected in current value

Question 3

how do excitable membranes show active behavior? what do they respond to?

Answer 3

respond to thrshold depolarization with an action potential: all or none, stereotyped sequence of V_m changes

Question 4

what is automaticity? what cells exhibit this?

Answer 4

cells that spontaneously & rhythmically generate action potentials

excitable cells that’re specialized to act as pacemakers do this

Question 5

point on an action potential when:

• threshold for initiatino
• reversal of membrane polarity at the peak
• afterhyperpolairzaiton before turn to Vm resting value

Answer 5

Question 6

what would the effect on depolarization of a membrane be if inward rectifiers close? why?

Answer 6

depolarization would be larger than expected b/c membraen conductance for K+ is reduced

Question 7

what controls resting potential of Vm in a neuron?

Answer 7

leak K+ channel

Question 8

what channels cause large spike in depolarization in a neuron?

Answer 8

opening of voltage-gated Na+ channels

Question 9

at hte peak of an action potential in a neuron, which channels are open?

Answer 9

voltage-gated K+ channels begin to activate

Na+ channels inactivate

Question 10

which channels repolarize the membrane? which phase?

Answer 10

voltage-gated K+ channels and leak K+ channels

during afterhyperpolarization

Question 11

what happens to the membrane to cause an action potential?

Answer 11

a strong enough stimulus depolairzes the membrane to threshold for an action potential initiation

result: rapid, lare depolarization

membrane then beings to repolarize

Question 12

which channels dominate at rest of action potential?

Answer 12

leak K+

Question 13

once Vm is depolarized to the threshold, which channels are in action?

Answer 13

voltage-gated Na+ channels open, drive Vm toward VNa

these channels begin to inactivate soon aftr peak of depolairzation

voltage-gated K+ channels also activate, repolarize the membrane

Question 14

which channels repolarize the membrane of an action potential

Answer 14

voltage-gated K+ channels

Question 15

what does Vm approach during afterhyperpolarization? why?

Answer 15

approaches Vk

because until voltage-gated K+ channels deactivate, K+ conductance is larger than it was in resting membrane, making Vm get close to Vk

Question 16

what kind of event is an action potential? what does this mean?

Answer 16

all or none - a stronger suprathreshold stimulus would cause Vm to reach threshold value more quickly, but wouldn’t change the shape of the subsequent action potential

Question 17

what and when is the absolute refractory period?

Answer 17

right after action potential, it’s impossible to initiate another one

some time is required for recently inactivated Na+ channels to de-inactivate before they can generate another action potential

period ends when full complement of Na+ channels has been de-inactivated

Question 18

what is state of channels during relative refractory pd? how might this show?

Answer 18

some Na channels have de-inactivated, but most have not

during this pd, may see small-amplitude, shallow slope spikes of Na+ channels as they de-inactivate

Question 19

when does the refractory period end?

Answer 19

when full complement of Na+ channels has been de-inactivated

then can launch full new action potential

Question 20

how does action potential travel down a neuron’s axon?

Answer 20

like a “wave” - action potential propagates down the axon

axon contains: leak K+ channels, voltage-gated and inactivating K+ and Na+ channels

1) voltage-gated Na+ channels open, Na+ enters cytoplasm, results in depolarization
2) depolarization spreads along membrane due to redistribution of charges per entry of uncompensated positive ions
3) per Na+ influx, K+ channels open, K+ exits cell through delayed rectifiers

membrane is repoalirzed, action potential terminated in that region

Question 21

what do all excitable heart muscle cells have in common?

Answer 21

1) long phase of depolarization compared to neurons
2) prominent use of Ca²⁺ as the depolarizing charge carrier

Question 22

are heart muscle cells usually depolarized or polarized? why?

Answer 22

usually depolarized

b/c mechanical pumping action of heart relies on contractions that last hundreds of milliseconds

Question 23

describe action potential of the ventricles

Answer 23

At rest, cells are polarized at about -90 mV; Kir channels dominant conductance

1) Phase 0: membrane depolarizes to threshold for action potential initiation; voltage-gated Na+ channels activated; rapid depolarization & upstroke
2) Phase 1: early/fast repolarization; Na+ channels inactivate
3) Phase 2: plateau; delayed opening of voltage-gated Ca²⁺ channels; voltage-gated K+ channels slowly activate
4) Phase 3: repolarization; K+ current builds via various voltage-gated K+ channels, and Ca2+ current diminishes as voltage-gated Ca2+ channels inactivate
5) Phase 4: diastole: begins after membrane returns to well-polarized resting potential

Question 24

what causes ventricular caridac muscle cell to return to its resting potential?

Answer 24

combination of voltage-gated Ca2+ channels inactivaing & voltage-gated K+ channels activating

Question 25

what are the different heart muscle cells, what is each responsible for?

Answer 25

pacemakers: impulse generation

His-purkinje: impulse propagation

“working” muscle: contraction

Question 26

what is normal sequence of events in cardiac cycle?

Answer 26

1) RA pacemaker cells spontaneously fire in the SA node, initiate an action potential
2) depolarization spreads through the atria, results in atrial contraction & stimulation of the AV node and His-Purkinje fibers that innervate ventricles
3) initiation, spread of action potentials in the ventricles, produces contraction that pumps blood to rest of the body

Question 27

what does an electrocardiogram (ECG) show?

what are the different parts of the line?

Answer 27

electrical activity of the various excitable cells & localization in the heart

1) 1st deflection: P-wave, depolarization of the atria, corresponds to Phase 0 of Atria
2) QRS complex, corresponds to Phase 0 of Ventricle
3) T-wave, corresponds to Phase 3 repolarization of ventricles

Question 28

what is the Q-T interval?

how long is it, normally?

Answer 28

the duration of the ventricular action potential and contraction

<450 ms normally

Question 29

what happens in a patient with long QT syndrome?

Answer 29

delayed, slow repolarization

can give rise to premature action potentials during Phase 3, without waiting for normal trigger from atria

can lead to dangerous arrhythmia, called torsade de pointes - ventricles contract in uncoordinated manner, independent of normal atrial rhythm; reduces pumping efficiency of heart

Question 30

what kind of pathology is LQTS?

Answer 30

“channelopathy,” pathology caused by mutation in a channel

Question 31

what cardiac channel mutations have been linked to LQTS?

Answer 31

1) voltage-gated Na+ channel; mutations impair inactivation, result in relative large inward current during plateau phase & deplayed repolarization
2) 2 of the voltage-gated K+ channels of Phase 3; causes delays and slows repolarization

Question 32

what happens in LQTS w/ overexpression of hERG?

Answer 32

hERG is a K+ channel; mutated G628S site in pore of the channel, reduces its conductance