L10 Heart- Myocardial EC Coupling Flashcards
Define the structural differences between cardiac and skeletal muscles.
Skeletal Muscle- fibers run full length of muscle, individual muscle cells innervated
Cardiac Muscle- small cells, syncytium (electrically coupled via gap jxn connections)
Define the functional differences between cardiac and skeletal muscles.
Skeletal Muscle- activated by ACh at NMJ, contraction NOT dependent on Ca influx (voltage sensor), contraction amp. Regulated by AP freq, summation and tetanus generates maximal tension, significant anaerobic metabolism
Cardiac Muscle- activated by cell-to-cell conduction (no NMJ), contraction dependent on Ca (CICR), contraction amp. Regulated by Ca influx via L type channels and SR Ca content, no summation or tetanus, primarily aerobic metabolism
What are the inotropic effects of catacholamines?
NE and Epi (symp) are positive ionotropic agents:
-Bind to B Adrenergic receptors, activating adenlyate cyclase= increase cAMP= activated PKA
PKA phosphorylates:
-Ca channels= increase Ca influx
-Phospholamban= increase SR Ca uptake
-Increase CICR
-Decreases time of relaxation
What are the inotropic effects of cardiac glycosides?
Digitalis is a positive inotropic agent used in CHF
- Inhibits Na/K pump
- Increase intracellular Na= decreased gradient
- Decrease Ca efflux via Na/Ca exchanger= increase intracellular Ca
- Increase in SR Ca content leads to greater SR Ca release and contraction
What are the inotropic effects of Ca channel blocking agents?
Verapamil, Diltiazem, Nifedipine are used as vasodilators and anti-arrhythmics
- Blocks Ca influx via Ca channels
- Decreases in SR Ca release and SR Ca content = less contraction of vascular smooth muscle (vasodilator)
- Cardiac anti-arrhythmic effects due to inhibition of L-type Ca current = inhibits conduction of AV node AP (blocks SVT)
- Side effect: Negative inotropic effects on heart
Define how HR affects the force of cardiac contraction (force-frequency relationship).
HR and rhythm (cycle length) affects contraction amp. B/c changes in time for intracellular Ca handling= changes in contractility
Define the cellular mechanisms underlying the contractile response to increase in HR.
Positive staircase (treppe)- as HR increase, strength of contraction increases
- Greater Ca influx per unit time and less time for Ca efflux via Na/Ca exchanger
- Increase SR Ca content and SR Ca release= larger contraction strength
- Do get a dip in contraction strength initially b/c there wasn’t enough time for Ca to get into SR with the speed up, then stores fill with the increase in Ca freq. and contraction increases
Define the cellular mechanisms underlying the contractile response to decrease in HR.
Negative staircase- as HR decreases, strength of contraction decreases
- Less Ca influx per unit time and more time for Ca efflux
- Decrease in SR Ca content and smaller CICR= smaller contraction strength
- Do get a spike in contraction initially b/c there is more time for the Ca to get into SR stores with the transition to slower HR, then Ca stores deplete with less Ca influx and contractions decrease
Define the cellular mechanisms underlying the contractile response to a premature beat.
Smaller than normal contraction
- Less time for recovery of L-type Ca current
- Less time for recover of SR Ca release channels
- Less time for redistribution of Ca stores in terminal cisternae of SR
- Smaller CICR = smaller contraction strength
Define the cellular mechanisms underlying the contractile response to the beat following a premature beat.
Post-extra systolic potentiation (PESP)- stronger than normal contraction of the beat following premature beat
- More time for recovery of Ca current
- More time for recover of SR Ca release channels
- More time for redistribution of Ca stores into terminal cisternae of SR
- Larger CICR= larger contraction strength
Define the function of sarcolemma in cardiac EC coupling.
Propogation of APs, controls Ca influx into cell via activation of T type Ca current
Explain the cellular mechanisms responsible for cardiac EC coupling.
- AP conducts along membrane and down T tubules.
- Depolarization of T tubules activates Ca influx (L type channels)
- Ca influx binds to and opens RyR
- Ca release from SR binds to troponin C to initiate contraction
- CICR
- Contraction maintained as long as cytosolic Ca remains elevated
- Relaxation is initiated when cytosolic Ca is removed by SR uptake, Na/Ca exchange, sarcolemma Ca pump
Define the function of T-tubules in cardiac EC coupling.
Transmits electrical activity to the cell interior, located at Z lines
Define the function of SR in cardiac EC coupling.
Intracellular Ca storage site.
Define the function of terminal cisterna in cardiac EC coupling.
Site where Ca influx triggers opening of Ca channels to initiate contraction (CICR)
