Question

Why is extracellular calcium needed in cardiac muscle contractions, and why is it important in delaying repolarization?

Answer 1

Cardiac muscles have cardiomyocytes composed of tubular myofibrils. These myofibrils have repeating sections of sarcomeres. Contraction of cardiac muscle requires calcium induced calcium release that is conducted via the intercalated disc. Cardiac cells are linked to each other by gap junctions.

Similar to skeletal muscle, the action potential occurs in the muscle cells of the ventricle by the entry of sodium ions across the sarcolemma. However, depolarization can only be sustained for longer duration when there is an inward influx of calcium ions. These calcium ions will flow via the L-type calcium channels. Cardiac muscle cells depend on calcium as they undergo a mechanism called calcium induced calcium release (CICR) from the sarcoplasmic reticulum occurring normal excitation-contraction (EC) coupling. EC coupling converts the electrical stimuli (action potential) to mechanical muscle contraction. CIRC occurs via its receptors within the cardiomyocyte. These receptors bind to calcium upon opening of calcium ion channels during depolarization. This causes release of more calcium ions into the cell.

When calcium concentration increases in the cell, calcium binds to troponin. This causes the actin binding sites on myosin to be free. There is ATP hydrolysis, ADP and PI binds to myosin head and Actin can then bind to myosin. Subsequently, there is cross bridge formation between actin and myosin, causing muscle contraction.

Cardiac muscle cell (ventricle) has four phases for generation of action potential and muscle contraction as follows:

Phase 4: Resting membrane potential is due to permeability of K+ ions through leaky K+ channels and voltage gated K+ channels at rest.

Phase 0: Rising phase of action potential caused by influx of Na+ via voltage gated sodium channels,

Phase 1-2: When the rising phase is over, the voltage-gated L type Ca+2 channel open and calcium will now enter the cell. This will produce a plateau of depolarization which depends on the balance between the calcium and the K+ channels, that are both open. The plateau phase is created by CICR, where the interior of cell is positive. Later, there is slow inactivation of Ca2+ channels. Longer the plateau of Calcium ions in the cell, the depolarization will continue and muscle cell cannot undergo repolarization. Depolarization results in generation of action potential

Phase 3: The voltage gated Ca2+ channels will inactivate, the K+ channels will dominate and the repolarization occurs, the voltage gated K+ channels will close and the membrane potential will reach phase 4.

Repolarization cannot occur till calcium ions channels are open. As calcium enters the cardiac muscle, it will generate a positive charge in the interior of the cell. Hence, membrane potential becomes more positive in the interior. This will allow depolarization to continue. Repolarization can only occur, when the inward influx of calcium ion is stopped by closing of the calcium channels.