ICL 2.0: Ionic Basis of Conduction, Cardiac Action Potential & Excitation-Contraction Coupling

Question 1

how does an action potential of cardiac myocytes work?

Answer 1

1. Na+ channels open and sodium comes into the cell depolarizing the cell from -90 mV to 20 mV
2. K+ channels open and K+ leaves the cell and drops the potential to 0 mV
3. Ca+2 channels also open and Ca+2 goes into the cell while K+ is leaving so there’s a plato
4. Ca+2 channels close but K+ stay open and K+ continues to leave and the action potential drops drastically from 0 back to -90 mV

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Question 2

what happens during phase 4 of the cardiac myocyte action potential?

Answer 2

resting phase = electrical diastole

cardiac myocyte the Potential (Gradient) = -90mV

Na+ and Ca++ channels are closed

K+ inward rectifier channels allow outward leak K+ (down concentration gradient)

Question 3

what happens during phase 0 of the cardiac myocyte action potential?

Answer 3

upstroke = depolarization

action potential from atrial fibers (Bachman’s Bundle) or Purkinje Fibers reaches ‘first myocyte’ and TMP starts to rise above -90mV

fast Na+ channels open time dependent Na+ leaks into cell (starts down concentration gradient)

the resting TMP rises to -70mV =threshold potential

now enough fast Na+ channels are open and large Na+ current into cell

rapid rise TMP to 0mV or above and fast Na+ channels close

Question 4

what happens during phase 1 of the cardiac myocyte action potential?

Answer 4

TMP just above 0mV (˜20 mV)

transient K+ channels open and K+ efflux out of cell

TMP reaches 0mV

Question 5

what happens during phase 2 of the cardiac myocyte action potential?

Answer 5

L-type Ca++ channels remain open and allows Ca++ influx

needed for contraction of cellular myofibrils

K+ channels (Delayed Rectifier) open K+ efflux down its concentration gradient

electrical balance = TMP plateau’s

Question 6

how does digoxin work?

Answer 6

it inhibits the Na/K ATPase and Na/Ca+2 pumps to keep Ca+2 inside the cell and increase heart contractions

Question 7

what happens during phase 3?

Answer 7

depolarization

Ca++ channels begin to close as delayed Rectifier K+ channels remain open allow K+ efflux K+ efflux exceeds Ca++ influx, Ca++ channels close

TMP re-approaches -90mV

Na+ ATPase and Ca++ ATPase carry Na+ and Ca++ out of cell

in addition, SR Na+-Ca++ exchanger carry Ca++ into SR (Electrical & Mechanical diastole= Relaxation)

concentration gradients become normal for resting potential

Question 8

how are cardiomyocytes connected?

Answer 8

gap junctions

allows for electrical signals to be conveyed and cells to be depolarized

Question 9

what is a refractory period?

Answer 9

AP of cardiac myocyte is a longer duration which allows more Ca++ entry = muscle contraction = SYSTOLE

the ‘redistribution’ of ions is therefore prolonged

during this time the channels are inactivated & refractory (variably) to a subsequent stimulation

long refractory periods are needed in cardiac myocytes to allow refilling of the chambers

during repolarization the refractoriness changes as more fast Na+ channels repolarize, bringing the cell membrane closer to its resting potential

thus, the degree of refractoriness = the number of fast Na+ channels to a resting state

there are 3 refractory periods: absolute, effective and relative refractory periods

Question 10

do atria or ventricles have longer refractory periods?

Answer 10

atria have shorter refractory period than ventricles

so atria are more sensitive to parasympathetic stimulation than ventricles

Question 11

how do action potentials work in the SA and AV nodes?

Answer 11

automaticity = spontaneous depolarization during Phase 4 in a rhythmic fashion

they still have to reach a threshold voltage to depolarize though same as the cardiac myocytes but the action potential is different = -60 mV

Phase 4 is a slow upward slope (not flat)

Phase 0 is less rapid, has lower peak amplitude

Phase 1 and 2 are absent in pacemaker cells

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Question 12

what happens during phase 4 of pacemaker action potentials?

Answer 12

diastolic phase between Depolarization

TMP at rest = -60mV

channels for fast Na+ current (INa) are continuously Inactivated

channels for funny current (If) open at -60mV allows Na+ influx
If (funny current) causes SLOW depolarization, activates voltage gated T-type Ca++ channels

at -60mV there is less K+ efflux, thus depolarization rather than repolarization

phase 4 is slowly upward, once reaches -40mV then depolarization can occur

thus, spontaneous gradual depolarization without neurotransmitter synapse or circulating stimulation/excitation

Question 13

what happens during phase 0 of pacemaker action potentials?

Answer 13

rapid depolarization!

less rapid upstroke

fast Na+ channels remain inactivated, & thus no current (INa)

max amplitude is LOWER than in cardiac myocytes

thus, Phase 0 = slow long-lasting Ca++ influx = ICa,L

Question 14

what happens during phase 3 of pacemaker action potentials?

Answer 14

repolarization!

Ca++ channels inactivated

K+ channels (Voltage gated) activated, K+ efflux ( IK [I Kr, I Ks] )

Question 15

what does chronotropic effect mean?

Answer 15

effects heart rate

Question 16

are there conditions in which a cardiac myocyte can acquire the ability to spontaneously depolarize?

Answer 16

if they’re ischemic or scarred/necrotic they can!

Question 17

do purkinje fibers have automaticity?

Answer 17

eh sorta

they depolarize at a much slower rate of 30-40 bpm which is good if the SA node stops working so you might see this if there’s heart block

they don’t have funny channels so they don’t have automaticity but they can if they have to

Question 18

activation of which receptor releases Ca+2 from the sarcoplasmic reticulum?

Answer 18

ryanodine

Question 19

activation of which receptor brings Ca+2 back into the sarcoplasmic reticulum from the cytoplasm?

Answer 19

SERCA

Question 20

what are the steps of sarcomere contraction?

Answer 20

1. activation of myosin head by ATP hydrolysis
2. cross-bridge formation between myosin and actin
3. phosphate release and power stroke
4. ADP release, ATP binding and actin filament release

Question 21

how does NE increase contractility?

Answer 21

Gs pathway increases cAMP which activates protein kinases that bring Ca+2 in and activate the ryanodine receptor