Question

Calcium plays a role during contraction of both skeletal and cardiac muscle, but there are important differences in the mechanisms leading to increased calcium concentration and contraction between both muscle types. Could you explain them?

Answer 1

Answer

The essential role of calcium in the initiation and development of contraction in heart muscle has become well established since the early experiments of Ringer who showed an absolute dependence of myocardial contraction on an extracellular source of calcium. It was later reported that in calcium-free solutions, isolated cardiac muscle retained excitability and could initiate and propagate action potentials although contractility was abolished. These findings established that extracellular calcium acted as an essential “coupler” of the excitation-contraction process.

Lüttgau and Niedergerke postulated that the calcium needed for contraction was stored in a specific “pool” in the myocardium which was somehow related to an extracellular compartment; with each action potential, a fraction of the stored calcium was released to participate in the contractile process.The mobilization of calcium from extracellular and/or intracellular sites to the contractile proteins involves processes modulated by a complex, interacting series of mechanisms that begin with excitation of the sarcolemma and ends when Ca2+ binds to troponin; this is the excitation-contraction coupling process.

During the course of a cardiac action potential, depolarization of the sarcolemma and T-system initiates calcium fluxes which are dependent upon an extracellular calcium source and which result in an increased concentration of ionized calcium within the cardiac cell. An increased permeability of the sarcolemma to calcium during the action potential plateau permits Ca2+ to move down its concentration gradient from outside to inside the cell via an electrogenic calcium-mediated current. In addition to the ionized calcium of the extracellular phase, it is thought by some that superficially-bound calcium of the sarcolemma is mobilized during depolarization and participates in the calcium flux associated with contraction.The amount of Ca2+ entering the cardiac cell during the plateau phase of the action potential is by itself probably insufficient to activate the myofilaments. Therefore, it has been proposed that the wave of depolarization and the influx of calcium may mediate the release of intracellular stores of bound calcium from the sarcoplasmic reticulum and possibly, under certain circumstances, from the mitochondria.The calcium mobilized from the above sources raises the concentration of ionized calcium above 10-7M in the area of the myofilaments, and calcium binding to troponin then initiates the chain of reactions which lead to actin-myosin complex formation and contraction of the myofibrils. Relaxation of the myocardium occurs when the calcium concentration around the myofilaments is reduced, primarily by an enzymatic uptake mechanism of the sarcoplasmic reticulum.

In skeletal muscle, beat-to-beat activation of the contractile elements is essentially independent of extracellular calcium. Therefore, the mode of E-C coupling is basically different from that of cardiac muscle with respect to the sources of activator calcium and the “trigger” by which the calcium is made available to the myofilaments. The classic studies of Winegrad provided detailed information about the source and sequence of Ca2+ movement during the E-C coupling process. Depolarization of the sarcolemma promotes the release of Ca2+ (by some as a yet undetermined mechanism, see below) from the lateral cisternae of the JSR (in the triad region over the Z-lines and A-bands) which activates the myofilaments to contract. Relaxation is initiated as Ca2+ and is sequestered by the longitudinal sarcotubules of FSR (in the region of the A-band). Once in the lumen of the FSR, it is thought that calcium may diffuse or be transported to the JSR for subsequent release during the next depolarization. This cyclic nature of Ca2+ fluxes in skeletal muscle during E-C coupling and relaxation is regarded as being strictly intracellular and independent of extracellular calcium.

Although cardiac muscle may have similar intracellular calcium fluxes, the details of such a cycle have not been confirmed. More important to the question of E-C coupling, however, is the nature of the coupling mechanism in both cardiac and skeletal muscle which initiates Ca2+ release from the SR.

Fig-Electromechanical coupling in cardiac and skeletal muscle.

Represented is a composite diagram of the relationship between simultaneously recorded transmembrane potentials (solid line) and isometric tension development (dashed line) to the relative time course of myoplasmic Ca2+ concentration (dotted line). Note different time scales for the two muscle types.