2 - Cardiac Muscle Flashcards
Cardiac Muscle: Fiber Structure
- Less Sarcoplasmic Reticulum (SR) than skeletal muscle
- T-Tubules
- Intercalated Discs
- Myofilaments form sarcomere
Purpose of intercalated discs in cardiac muscle?
- Ties cardiac muscle cells together (mechanical) - Adherens Junctions/Desmosomes
- Electical connections allow propagation of action potential through heart - Gap Junctions permit ion flow
***Mechanical and Electrical Coupling***
Electrophysiology in Cardiac Cells
Phase 4
- Resting potential
- Sodium and Calcium channels closed
- 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
Electrophysiology in Cardiac Cells
Phase 0
Fast sodium channels open when membrane rapidly depolarized
Quick opening, close to inactive state, return to closed resting state when membrane repolarizes
Electrophysiology in Cardiac Cells
Phase 1
Partial repolarization, due to:
- Efflux of [K] through transient outward channels
- Inactivation of sodium channels
Electrophysiology in Cardiac Cells
Phase 2
Plateau Phase
- L-type calcium channels open for long time
- Calcium influc gradual (vs Phase 0)
- Trigger internal calcium release from SR
- Potassium channels close
**Plateau caused by combination of decreased Potassium efflux, and increased Calcium Influx**
Electrophysiology in Cardiac Cells
Phase 3
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
Electrophysiology in Cardiac Cells
Ion Channel Summary
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
Slow Response Action Potential (Pacemaker Cell Action Potentiona)
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 (If or “Funny Current”) and Influx of Sodium Ions through Slow Channel
Slow Response Action Potention:
Phase 0
Less rapid–no fast sodium channels, depends on both L and T type calcium channels
Slow Response Action Potentials:
Differences in Phase 1/2?
No phase 1/2
Refractory Period in Cardiac Muscle
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
Effective vs Relative Refractory Period
Effective - Phase 0-2, Part of 3 = No AP
Relative - Phase 3 = Can generate AP with large stimulus, but weak/slow
**Cardiac Muscle Contraction - Key Requirements**
Extracellular Calcium
Acts as trigger to stimulate release of large amounts of calcium from SR
Cardiac Muscle Excitation-Contraction Coupling
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
Skeletal Muscle Contraction Mechanism
Rest
Contraction
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
Cardiac Muscle Relaxation
Calcium Influx ends at Phase 2-3
Calcium pumped into SR by SERCA
Phospholamban Protein
Phospholamban Protein
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
Regulation of Contraction (Inotropy)
Force of contraction depends on intracellular calcium
Modulate Calcium by:
- Entry of Ca2+ into cell
- Calcium release by SR
- SERCA levels
- Calcium Efflux
B-Adrenergic Signaling in Cardiac Muscles
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
Cholinergic Signaling in Cardiac Muscle
Reduces Heart Rate
Parasympathetic Nervous System
ACh binds to Mucarinic M2 Receptors; reduces calcium levels
Ventricular Cells less sensitive than atrial cells
Na, K, ATPase and Cardiac Glycosides - Digozin, Ouabain
Leads to greater contractions
Inhibits ATPase, intracellular sodium levels rise, less calcium removed = more calcium inside cell
Cardiac Muscle Length-Tension Relationship
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
Cardiac Muscle Length/Tension Relationship
Stretch of Sarcomere results?
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
