Electrophysiology, Excitation, and Contraction Coupling

Question 1

Sequence of Cardiac Electrical Activation

Answer 1

SA Node

Atrium

AV node

Bundle of His

Purkinje Fibers

Ventricles

Question 2

Which action potentials are similar in the heart, which are unique? SA node, atrium, AV node, Purkinje fibers, ventricle

Answer 2

SA node similar to AV node.

Atrium unique

Ventricle similar to purkinje fibers

Question 3

Where is this AP taken? What are the phases called? Explain the movement of ions during each of the phases.

Answer 3

Ventricular AP.

Phase 0: Upstroke, Na+ influx

Phase 1: Notch, Na in, K out

Phase 2: Plateau, Ca in, K out

Phase 3: Repolarization, K out

Phase 4: Resting potential, K out, NCX in

Question 4

What is the resting potential of a ventricular myosite vs an SA node myosite?

Answer 4

-85 mV vs -60 mV

Question 5

Where is this AP taken? What ion movements are responsible for each phase?

Answer 5

From SA node

Phase 0: Ca influx

Phase 2: Ca in and K out

Phase 3: K out

Phase 4: NCX and I_f

Question 6

Differences between SA nodal firing and ventricular firing?

Answer 6

SA nodal firing occurs spontaneously, ventricular firing does not.

Phase 0 is much faster in ventricle!

Phase 1 is absent in SA node

Plateau (phase 2) is subtle and abbreviated in SA node

Phase 3: Same

Phase 4: Voltage increases in SA node and is less negative.

Question 7

Absolute vs Relative Refractory Period

Answer 7

ARF: Impossible to trigger second AP

RRP: Strong stimuli trigger weak APs.

Question 8

What is negative current in a whole cell clamp experiment?

Answer 8

Positive charge flowing inward

Question 9

V=IR

Answer 9

It’s true.

Question 10

Equilibrium potential of K, Na, Ca

Answer 10

K= -89

Na= +70

Ca= +133

Question 11

Driving force

Answer 11

DF= V- Equilibrium potential

Question 12

What happens if V=Ex, V-Ex>0, V-Ex<0?

Answer 12

V=Ex: No ion movement

V-Ex>0: Positive current (cation moves out)

V-Ex<0: Negative current (cation moves in)

Question 13

What ion does this represent? Why?

Answer 13

Sodium, look at reversal potential around +70.

Question 14

What ion does this represent?

Answer 14

L-type calcium current, activates and inactivates more slowly than sodium

Question 15

Role of L-type Ca current in ventricular myocytes

Answer 15

Plateau of action potential, initiate SR calcium release

Question 16

Role of L-type Ca current in SA and AV nodal myocytes

Answer 16

Action potential upstroke (phase 0)

Question 17

Why do Calcium channel blockers (Type IV antiarrhythmics, antihypertensives) have multiple bad effects?

Answer 17

Because Ca channels present in many diverse tissues.

Question 18

Which ion and channel does this represent?

Answer 18

Current through KIR Channel (I_K1)

Question 19

Purpose of KIR

Answer 19

Stabilizes resting potential around ~85mV, also responsible for long plateau when it inactivates

Question 20

What do these represent?

Answer 20

Delayed rectifier K currents.

Rapid I_Kr

Slow I_Ks

Responsible for repolarizing membrane after plateau

Question 21

Funny Current

Answer 21

I_F occurs in SA node, channel is open at very negative voltages, but opens at more positive voltages. Caused by mostly sodium (some K) going in. Supplies depolarizing current to drive voltage upward in SA node.

Question 22

Where is KIR located?

Answer 22

In ventricle, not in SA node

Question 23

Why is upstroke (phase 0) so much faster in ventricle?

Answer 23

Because of I_Na, which is not present in SA node. There, the upstroke is caused by I_Ca, which is very slow

Question 24

Which cardiomyosites have delayed rectifier K channels?

Answer 24

SA and ventricle

Question 25

How do the concentrations of calcium in the SR and cytosol compare?

Answer 25

SR concentration is MUCH higher (10,000x)

Question 26

CICR

Answer 26

Calcium Induced Calcium Release. Can't have release of Ca from SR without calcium. Required for contraction.

Question 27

Steps of EC coupling in cardiac muscle

Answer 27

Excitation is coupled to contraction. First, depolarization causes L-type calcium current. Ca binds to ryanodine receptors in the SR membrane, which releases 4x more calcium, which causes contraction by binding to troponin.

Question 28

How is such a large concentration of Ca built up in SR?

Answer 28

SERCA, transports Ca in using ATP

Question 29

NCX

Answer 29

3 Na in along gradient, 1 Ca out against gradient

Question 30

EC coupling in skeletal muscle

Answer 30

NAChR opening causes influx of sodium, which induces action potential in muscle cell, which causes activation of Ltype Ca channels that are **bound directly** to ryanodine receptors. **NO extracellular CA influx necessary.**

Question 31

How does Ca influx induce contraction in cardiomyocytes if they are so huge?

Answer 31

T tubules (membrane invaginations) extend into cell interior. This way, calcium that surrounds the cell can sit near interior.

Question 32

T Tubules and RyR location

Answer 32

RyRs sit close to T tubules so calcium doesn't have to diffuse too far in order to cause CICR.

Question 33

How does the cardiac myocyte relax after contraction?

Answer 33

70% of calcium is pumped back into SR, 20% pumped out via NCX.

Question 34

In steady state conditions, total amount of Ca entering through L type Ca current must equal... Total amount of Ca released via RyRs must equal...

Answer 34

Total amount of Ca exiting via NCX Total amount resequestered by SERCA

Question 35

How is strength of contraction modulated?

Answer 35

By altering the amount of Calcium stored in the SR. Also, the effect is nonlinear.

Question 36

What happens in non-steady state conditions? When does this happen?

Answer 36

Total Ca entering different than total amount exiting. This causes more IC calcium, more in SR. Causes bigger contractions. This happens during exercise.

Question 37

Can RyRs randomly and spontaneously release Ca?

Answer 37

Yes. Usually these effects are harmless and localized, but it can be bad sometimes!

Question 38

What happens when multiple RyRs open spontaneously?

Answer 38

High IC calcium can diffuse to other RyRs causing increased opening. This will increase IC Ca some more, and the NCX will have to work harder. This can create a depolarizing current due to the fact that more sodium in brought into the cell, causing inappropriate action potentials.

Question 39

DAD

Answer 39

Delayed after depolarization. One is okay usually, but more can initiate aberrent action potential.

Question 40

Cellular correlates of heart failure

Answer 40

Weaker contractions, slower relaxation. Caused by **downregulation of SERCA.** So, less Ca is pumped into the SR, less released, smaller contractions. Also, disrupted T-tubule structure, which causes increased distance to ryanodine receptors.

Question 41

Digitalis

Answer 41

Na-K pump inhibitor. Used in heart failure. Inhibition causes increased IC Na, so NCX is less effective. More intracellular Ca, which is pumped into SR. This causes stronger contractions upon release. But can lead to arrhythmias.

Question 42

Positive Inotropy

Answer 42

Stronger contractions