Lecture 10: Excitation-Contraction Coupling (Hayward) Flashcards
What triggers myocardial force production?
Ca influx via channels in sarcoplasmic reticulum. Ability of heart to contract is influenced by extracellular conc. of Ca
What do actin/myosin need to contract?
Ca (takes away an inhibition that prevents their interaction)
What is essential for intracellular Ca++ release?
Extracellular Ca release
What terminates Ca influx?
repolarization
duration of AP is fx of:
speed of Ca channels
What triggers relaxation of myocardial muscle?
Activation of Ca/ATPase Pump by phosphorylation of phospholambin
What trigger phosphorylation of phospholambin? (2)
Increases in intracellular Ca++
Increases in cAMP levels
Calmodulin
Inhibits further Ca release as Ca/ATPase is activated to get rid of Ca and relax cardiac muscle
Ca/ATPase
pump that removes Ca into extracellular space to induce muscle relaxation. Activated by phosphorylation of phospholambin. Inhibited at rest
Why is it important to start reuptaking Ca as soon as its released?
To ensure duration of contraction follows period of depolarization only
3 main mechs of Ca removal:
1) Na/Ca exchanger and Ca pump in the plasma membrane both extrude Ca from space into extracellular space (80%)
2) Ca pump sequesters Ca within SR
3) Ca is bound in the SR by calreticulum and calsequestrin
2+3 = 20%
What does digitalis drug manipulate
inhibits Na/K ATPase, causing buildup of intracellular Na and decreasing concentration gradient for Na/Ca exchanger
Where is MOST Ca sequestered?
SR
Na/Ca exchanger**
Forces 1 Ca++ out, 3 Na+ into cell **
Force production in cardiac vs. skeletal muscle
skeletal —> by changing numbers of AP to muscle over a period of time (more AP = more force)
cardiac –> change intracellular Ca concentrations (more Ca = stronger/longer AP)
Mechanisms that can raise or lower intracellular Ca concentration can therefore modulate:
contractile force/systolic force production in heart
How to increase heart contractility?
bring more Ca into cell from surface and release more into cell from SR
very high Ca concentration can induce:
cardiac arrest in systole (muscle can’t relax)
What parts of heart does sympathetic system affect? ***
SA node, AV node, cardiac tissue ***
What parts of heart does parasympathetic system affect? ***
Pacemaker cells ***
What receptor activation increases Ca opening in myocardial cells?
beta-1 (via SYMPATHETIC stimulation)
sympathetic effect on Ca release and sequestration
Quickens release AND reuptake of Ca. Increases contractility.
Parasympathetic effect on Ca release and sequestrian
little direct effect
time-dependent accumulation of Ca
increases in HR result in more Ca influx and less time for Ca removal
How does external Na concentration effect RMP?
It doesn’t. RMP is independent of this (depends mainly on K)
What DOES Na+ concentration influence in heart?
AP, contractility
Decreased Na outside cell –> conc. Ca inside cell?
increased
Increased Na inside cell –> conc. Ca inside cell?
increased
What is rate of heart relazation most dependent on?
how quickly Ca++ can be re-sequestered
Methods of cytosolic C++ release
1) extracellular influx through Ca channels
2) Ca triggered Ca release from SR
3) Na/Ca exchanger
Methods of cytosolic Ca decrease
1) SR reuptake
2) Ca ATPase pump on sarcolemma
3) Na/Ca exchanger
transverse tubule system
invaginations of sarcolemma which help transfer the AP to the inner part of the muscle membrane. Most prominent in ventricular muscle and atria muscle
