Increasing intracellular sodium triggers calcium release from bound pools

Abstract

AN increase in the free ionised cytosolic Ca²⁺ concentration is generally regarded as the critical event necessary for the induction of exocytotic release of neurotransmitters and hormones from excitable cells. Stimulation of such cells is thought to result in an alteration of the membrane permeability to Ca²⁺ with a subsequent flow of Ca²⁺ ions down their gradient into the cytosol from the extracellular space¹. In addition, release of Ca²⁺ from intracellular compartments–notably the mitochondria—mediated by a rise in intracellular cyclic AMP may also, in some systems, result in an increase in the cytosolic Ca²⁺ concentration and thus to exocytotic release². Recent evidence suggests that small increases in Na⁺ concentration may release Ca²⁺ from mitochondria isolated from cardiac muscle cells³. Conversely, the uptake of Ca²⁺ into mitochondria of squid axoplasm is reduced by elevated sodium⁴. Since increases in the internal Na⁺ concentration occur during stimulation of many excitable cells, it is feasible that Na⁺ could act as a physiological releaser of Ca²⁺ from intracellular stores. We have obtained evidence for this possibility from studies designed to examine the role of Na⁺ in the calcium-dependent exocytotic release of insulin from the pancreatic β cell.