Regulation of cardiac muscle contraction

• Graded contractions

• Effect of cardiac muscle stretching

• Channel activity during action potentials– In myocardial contractile cells– In autorhythmic pacemakers

Graded contraction

• The amount of force varies with the number of cross-bridges formed

• Low Ca++ few cross-bridges

• High Ca++ more cross-bridges

The effect of epinephrine and norepinephrine of contraction

• NE and E bind to beta 1 receptors on contractile myocardial cells

• The beta 1 receptor is coupled to a G protein

• Cyclic AMP is formed

The effect of epinephrine and norepinephrine of contraction

• cyclic AMP is formed

• 1. Voltage gated Ca++ channels are phosphorylated stay open longer more intracellular Ca++ stronger contractions

• 2. A regulatory protein, phospholamban, is phosphorylated increased activity on SR Ca++ ATPase contractions shorten duration

Effect of phospholamban on Ca++ release

• NE and E activityincrease phospholamban activity increase Ca++ ATPase activity on SRmore Ca++ is sequestered into the SRmore Ca++ is available for Ca++ release

during stimulationstronger force of contraction

Effect of NE and E on contraction

• Stronger, more frequent contractions

When myocardial cells elongate

• The amount of Ca++ entering the myocardial cells may increase

the force of contraction increases

Myocardial contractile cell action potentials

• Resting potential is stable -90 mV• Wave of depolarization through gap

junctions• Voltage gated Na+ channels open• Voltage gated K+ channels open• Slow voltage gated Ca++ channels open

and K+ channels close• Ca++ channels close and K+ channels

open

Long action potential

• Myocardial cell refractory period and contraction end simultaneously

Action potentials in myocardial autorhythmic cells

• The channels:– If channels allow passage of Na+ and K+

– Ca++ channels

Action potentials in myocardial autorhythmic cells

• Unstable resting membrane potential• Pacemaker potential• At a membrane potential of -60 mV Na+

enters through the If channels mb depolarizes Ca++ channels open Ca++ channels close K+ leaves

Modulation of autorhythmic cells

• NE (sympathetic) and E (adrenal hormone)

• Autorhythmic cells have beta1 receptors• Cyclic AMP levels increase• Properties of If and Ca++ channels altered• More rapid Na+ and Ca++ entry• Rapid action potential• Rapid contractions

Modulation of autorhythmic cells

• Parasympathetic, acetyl choline

• Muscarinic receptors

• K+ channels open mb hyperpolarizes cell less excitable

• Ca++ channel less likely to open slower depolarization cell is less excitable