2 - Cardiac Muscle

Question 1

Cardiac Muscle: Fiber Structure

Answer 1

• Less Sarcoplasmic Reticulum (SR) than skeletal muscle

- T-Tubules

• Intercalated Discs

- Myofilaments form sarcomere

Question 2

Purpose of intercalated discs in cardiac muscle?

Answer 2

1. Ties cardiac muscle cells together (mechanical) - Adherens Junctions/Desmosomes
2. Electical connections allow propagation of action potential through heart - Gap Junctions permit ion flow

***Mechanical and Electrical Coupling***

Question 3

Electrophysiology in Cardiac Cells

Phase 4

Answer 3

1. Resting potential
2. Sodium and Calcium channels closed
3. Potassium Channels open

Extracellular [Na] > Intracellular [Na]

Extracellular [K] < Intracellular [K]

Sodium removed by Na-K-ATPase

Calcium removed by sodium-calcium exchanger and calcium pump

Question 4

Electrophysiology in Cardiac Cells

Phase 0

Answer 4

Fast sodium channels open when membrane rapidly depolarized

Quick opening, close to inactive state, return to closed resting state when membrane repolarizes

Question 5

Electrophysiology in Cardiac Cells

Phase 1

Answer 5

Partial repolarization, due to:

1. Efflux of [K] through transient outward channels
2. Inactivation of sodium channels

Question 6

Electrophysiology in Cardiac Cells

Phase 2

Answer 6

Plateau Phase

1. L-type calcium channels open for long time
2. Calcium influc gradual (vs Phase 0)
3. Trigger internal calcium release from SR
4. Potassium channels close

**Plateau caused by combination of decreased Potassium efflux, and increased Calcium Influx**

Question 7

Electrophysiology in Cardiac Cells

Phase 3

Answer 7

Potassium exits through delayed rectified channels

Potassium efflux exceeds calcium influx

Calcium channels close, leads to all potassium efflux

Retuns membrane back to resting potential

Question 8

Electrophysiology in Cardiac Cells

Ion Channel Summary

Answer 8

0 = Na Channels Open

1 = Na Channels Close

2 = Ca2+ Channels Open; Fast K+ Channels Close

3 = Ca2+ Channels Close; Slow K+ Channels Open

4 = Resting Potential

Question 9

Slow Response Action Potential (Pacemaker Cell Action Potentiona)

Answer 9

Can initiate depolarization without external signal

Differs from fast response cells–resting potential less negative; causes fast sodium channels to be inactivated

Spontaneous gradual depolarization during Phase 4–caused by Pacemaker Current (I_f or “Funny Current”) and Influx of Sodium Ions through Slow Channel

Question 10

Slow Response Action Potention:

Phase 0

Answer 10

Less rapid–no fast sodium channels, depends on both L and T type calcium channels

Question 11

Slow Response Action Potentials:

Differences in Phase 1/2?

Answer 11

No phase 1/2

Question 12

Refractory Period in Cardiac Muscle

Answer 12

Action potential lasts longer than skeletal muscle

Period where AP can’t fire–allows ventricles to empty and refill

*Due to inactivation of Fast Sodium Channels

Question 13

Effective vs Relative Refractory Period

Answer 13

Effective - Phase 0-2, Part of 3 = No AP

Relative - Phase 3 = Can generate AP with large stimulus, but weak/slow

Question 14

**Cardiac Muscle Contraction - Key Requirements**

Answer 14

Extracellular Calcium

Acts as trigger to stimulate release of large amounts of calcium from SR

Question 15

Cardiac Muscle Excitation-Contraction Coupling

Answer 15

During Phase 2, Calcium enteres through L-ype channels in T-tubules and sarcolemma; similar to DHP receptors

Entry of Ca2+ activates RyR2 channels in SR (calcium gated)

Calcium released from SR

Question 16

Skeletal Muscle Contraction Mechanism

Rest

Contraction

Answer 16

Rest - Tropomyosin blocks myosin binding site on actin

Contraction - Calcium binds to troponin C, changes conformation of complex–myosin can bind to actin

All same as skeletal muscle

Question 17

Cardiac Muscle Relaxation

Answer 17

Calcium Influx ends at Phase 2-3

Calcium pumped into SR by SERCA

Phospholamban Protein

Question 18

Phospholamban Protein

Answer 18

Found in SR membrane, when phosphorylated (activated) by cAMP-dependent kinase, inhibition removed

SERCA more active

Less calcium available, promotes relaxation

But more calcium available next time = stronger next contraction

Question 19

Regulation of Contraction (Inotropy)

Answer 19

Force of contraction depends on intracellular calcium

Modulate Calcium by:

1. Entry of Ca2+ into cell
2. Calcium release by SR
3. SERCA levels
4. Calcium Efflux

Question 20

B-Adrenergic Signaling in Cardiac Muscles

Answer 20

Sympathetic Nervous System stimulates, catecholamines released–bind to B1-adrenergic receptors

Leads of activaion of PKA, opening calcium channels; also phospholamaban (SR uptake of Ca)

Net = Increase in Contraction and Relaxation = Increase Heart Rate

Question 21

Cholinergic Signaling in Cardiac Muscle

Answer 21

Reduces Heart Rate

Parasympathetic Nervous System

ACh binds to Mucarinic M2 Receptors; reduces calcium levels

Ventricular Cells less sensitive than atrial cells

Question 22

Na, K, ATPase and Cardiac Glycosides - Digozin, Ouabain

Answer 22

Leads to greater contractions

Inhibits ATPase, intracellular sodium levels rise, less calcium removed = more calcium inside cell

Question 23

Cardiac Muscle Length-Tension Relationship

Answer 23

Stretching sarcomere increases force of contraction (Frank-Starling Law)

Helps pump volume of blood received

Preload - Increased stretch prior to contraction INCREASES force generation during contraction

Normally operate lower than maximum preloads, allows heart to meet demands of increased work

May be due to titin, more ECM, proximity of actin/myosin

Question 24

Cardiac Muscle Length/Tension Relationship

Stretch of Sarcomere results?

Answer 24

Increase sensitivity of Troponin C to Calcium, increases rate of cross-bridge attachment and detachment

Decrease tension comes from disruption of myocardial fibers, not decrease of crossbridges