Relaxation in heart muscle: some morphological and biochemical considerations

Abstract

In striated muscle the transition from the active to the resting state requires a reduction in the cytosolic concentration of ionized calcium (Ca2+), achieved by a rapid sequestration into the sarcoplasmic reticulum and the return of some Ca2+ to the extracellular phase. Morphologically the sarcoplasmic reticulum (SR) is heterogeneous. Specialized regions occur whenever the limiting membranes of the SR approach those of the plasmalemma. These specializations include a narrowed lumen, relative to that found in non-specialized parts of the SR, the presence of electron-dense 'feet' extending into the junctional gap separating the facing membranes of the plasmalemma and the SR, and the occurrence of intraluminal densities. These specializations can assume a variety of configurations, some of which appear to be species specific. The accumulation of Ca2+ by the SR, is a rapid process and the required energy is derived from the hydrolysis of ATP via a Ca2+-activated ATPase in the limiting membranes of the SR. Impaired relaxation in heart muscle can result either from an inadequate supply of ATP, Ca2+-overload, failure of the Ca2+-activated ATPase enzyme, leakage of Ca2+ from the SR, or the failure of the cell to return Ca2+ back into the extracellular phase. Evidence will be presented to show that the rise in resting tension that is caused by an inadequate supply of oxygen involves a mobilization of Ca2+ from the internal stores, and insufficient ATP to drive the ATPase enzyme in the SR, rather than a malfunction of the enzyme. Likewise ouabain-induced contractures have been found to be associated with diminished tissue stores of ATP, the rise in tissue Ca2+ occurring as a late phenomenon.