Heart Lecture 1: Cardiac Resting Membrane and Action Potential

Question 1

Formula for cardiac output

Answer 1

heart rate x stroke volume

Question 2

Stroke volume

Answer 2

amount of blood pumped per beat

Question 3

Resting heart rate

Answer 3

72 beats per minute

Question 4

Canonical conduction pathway

Answer 4

SA node –> internodal pathways –> AV node –> bundle of His –> bundle branches –> Purkinje fibers

Question 5

Where is the most rapid conduction found?

Answer 5

Purkinje fibers (needs to activate all cells at once)

Question 6

How long does it take to activate the whole heart, from the endocardium to the epicardium?

Answer 6

100ms

Question 7

Which interval is referred to as the AV nodal conduction time?

Answer 7

PR interval

Question 8

Why is the resting potential of a myocyte slightly more positive than the equilibrium potential of potassium?

Answer 8

Na+ leakage into the cell (makes it more positive) makes Vm = -90mV not -100mV

Question 9

What maintains ionic concentrations within the cell?

Answer 9

1) Na+,K+-ATPase (3 Na out, 2 K in –> net outward + charge)

2) Na+/Ca++ exhange (3 Na in, 1 Ca out –> net inward + charge)

Question 10

Function of digitalis?

Answer 10

to inhibit the Na, K-ATPase and therefore increase the contraction of the heart

Question 11

Function of Na, Ca exchanger?

Answer 11

to keep intracellular calcium low (pumps one out, against its concentration gradient, for the passive import of 3 sodium ions into the cell)

Question 12

Normal extracellular potassium levels?

Answer 12

3-5mM

Question 13

Normal intracellular potassium levels

Answer 13

150mM

Question 14

What is inward (anomalous) rectification?

Answer 14

a decrease in K+ permeability (meaning channels (like IK1) are likely shut) that occurs when the electrical or chemical driving force of K+ is increased

Question 15

What two scenarios increase the driving force on K+? (Hint: one is chemical and the other is electrical)

Answer 15

1) decrease in extracellular [K+] (therefore increasing the gradient)
2) depolarization of the membrane potential (makes inside of cell more positive so a positive ion like K would want to get out)

Question 16

What is the clinical importance of anomalous rectification?

Answer 16

creates a plateau when cell resting potential gets to be more positive

normally, in a nerve action potential, K+ channels immediately open and charge flows out when the membrane potential becomes more positive - not the case immediately with cardiac myocytes

Question 17

Effects of hyperkalemia on action potential?

Answer 17

depolarizes resting membrane potential (MAKES IT MORE POSITIVE)

1) increases membrane [K+] permeability (more channels should be open)
2) decreases K+ conc gradient across membrane (fewer ions travel since extracellular environment is more similar to intracellular)

Question 18

Effects of hypokalemia on action potential?

Answer 18

No net effect

1) decreases membrane [K+] permeability (IK1 channel shuts down)
2) increases [K+] gradient across membrane (greater motivation for K+ ions to move but they don’t)

Question 19

Heart tissue that act via FAST APs

Answer 19

atrial and ventricular muscle

Question 20

Heart tissue that act via SLOW APs

Answer 20

SA and AV node

Question 21

Phases of Fast APs

Answer 21

0 = upstroke (net Na+ movement into the cell)
1 = initial repolarization (ITO K+ channel opens allowing net K+ out of cell; Na+ channels close)
2 = plateau (more Ca++ entering the cell and background conductance of K+ decreases via IK1, inward rectifier)
3 = repolarization (IK, delayed rectifier, opens and K+ flows out of the cell)
4 = resting potential achieved

Question 22

Phases of Slow APs

Answer 22

0 = upstroke (slow upstroke due to Ca++ influx into cell)
3 = repolarization (K+ efflux from cell)
4 = resting potential sloped because these cells are always active

*no fancy initial repolarization or plateau

Question 23

Why is the slow AP slower than the fast APs?

Answer 23

Slow tissue is calcium dependent - Ca++ channels are slower to activate than Na+

Question 24

Difference between Ca++ activation in cardiac muscle and skeletal muscle?

Answer 24

Skeletal: Ca++ current is electrically connected to ryanodine receptor on sarcoplasmic reticulum - no net Ca++ influx into the cell

Cardiac: Ca++ flows directly into cell and induces Ca++ release from reticulum

Question 25

How does the plateau occur in fast action potentials and why is it important?

Answer 25

It occurs because the inward rectifier (IK1) decreases K+ flow when the cell is very positively charged (depolarized). If it did not, K+ would pour out of the cell immediately and there would be no delay for the delayed rectifier IK K+ channel to open

plateau allows for refractory period which allows for contraction

Question 26

What does tetradotoxin (TTX) do?

Answer 26

blocks the fast Na+ channels impairing fast APs

Question 27

How can we physiologically mimic the effects of TTX?

Answer 27

depolarize the membrane (hyperkalemia)

Question 28

How does TTX allow the slow APs to take over?

Answer 28

blocks the mechanism of fast upstroke (Na+) so untouched Ca++ channels take over

Question 29

When would fast responses change to slow responses clinically?

Answer 29

after an MI, slowing conduction dramatically