Mechanical Activity of Myocardial Contractile Cells

Question 1

define excitation-contraction coupling

Answer 1

the process by which membrane depolarization leads to contraction

Question 2

compare and contrast excitation-contraction coupling in cardiac and skeletal muscles

Answer 2

1. in skeletal muscle, no extracellular/trigger calcium is required
2. in both, an increase in cytosolic calcium is required for actin/myosin interaction and contraction is regulated by thin filaments

Question 3

describe the role of Ca2+ ions in the regulation of cardiomyocyte contraction

Answer 3

increase in cytosolic Ca2+ is integral to myocyte contraction and there are 2 fluxes required:

1. trigger calcium makes up 20% of calcium; extracellular origin, moves in through VG L=type Ca2+ channels (dihydropuridine receptors) during plateau/phase 2 of AP in response to membrane depolarization
2. calcium from sarcoplasmic reticulum/calcium-dependent calcium release in response to trigger calcium moves through calcium release channels (ryanodine receptors) on SR down their concentration gradient; makes up the other 80%

Question 4

understand the temporal relationship between the surface ECG events and myocardial contraction

Answer 4

1. the P wave represents atrial depolarization, and occurs shortly before the action potential (phase 4 and 0) is propagated
2. this depolarization causes the QRS complex, as the AP spreads to the ventricles and the ventricles depolarize, representing early repolarization ad the plateau phase until
3. the T wave represents ventricular repolarization and occurs as contraction is recorded on the ECG

Question 5

list and describe the two major mechanisms for recruitment of cardiac inotropic reserve

Answer 5

1. changes in whole organ performance: length-dependent stretch mechanisms (Starling), important for beat to beat regulation
2. changes in cellular contractile properties: modifying interactions between actin and myosin; important for sustained hemodynamic challenges such as exercise (sympathetic phosphorylation)

Question 6

explain starling’s law of the heart

Answer 6

the greater the stretch on myocytes at end of diastole (the greater the preload) the greater the force of contraction

Question 7

explain the ways in which activation of the sympathetic nervous system increases myocardial contractility

Answer 7

1. norepinephrine/epinephrine bind B1-adrenergic receptors on myocyte
2. receptor binding leads to increased cAMP, a second messenger that leads to increased activity of protein kinases
3. protein kinases add phosphate groups to various proteins to result in:
   more trigger Ca2+ to interact with SR by phosphorylating VG L-type calcium channels
   increased calcium release by SR by phosphorylating ryanodine receptors
   greater number of actin-myosin interactions by phosphorylating myosin
   increased calcium uptake by SERCA pump to yield more calcium available for next beat by phosphorylating phospholamban