A calcium transport system for mammalian cells

Abstract

Several decades ago, Heilbrunn showed that the microinjection of a small amount of inorganic calcium into a muscle cell caused contraction of the muscle (1). Since then it has been shown that not only are steady state conditions of many types of cells affected by intracellular calcium concentration (2), but specialized responses evoked by specific stimuli and associated with movement of calcium into the cell (3) can be induced directly by increasing intracellular calcium. For example, calcium ionophores cause insulin secretion by pancreatic islet cells (4), histamine release from basophils (5) and blast transformation of human lymphocytes (6). These findings suggest that one of the necessary steps in the chain of events initiated by the physiological stimulus (e.g. release of histamine from basophils when specific antigen reacts with cell-bound IgE) is a local increase in calcium ion concentration. The physiological role of calcium has been studied most extensively in heart and skeletal muscle. It is now well established that the concentration of free calcium ions inside cells is very low compared to extracellular fluid (7,8). A minimum system for achieving this is a limited cell membrane permeability to calcium and an active transport system for pumping calcium out of the cell. In this review we will present the thesis that mammalian heart and skeletal muscle have in addition a calcium transport system (CTS) which is located external to the electric membrane, is oriented opposite to the cell membrane calcium pump (i.e. pumps toward the cell) and establishes a microdomain immediately external to the electric membrane in which calcium concentration is maintained higher than in the rest of the extracellular space. Since this system is assembled on the outside of the cell, from components circulating in the blood plasma, we have had a unique opportunity to isolate and characterize them. Thus we were able to avoid extraction from the cell membrane structure, the difficult first step facing students of other transport systems.