| Summary: | A study has been made of the involvement of metabolism in the regulation of net Ca movements and permeability to alkali ions in human red cells. Experiments were done to determine whether or not net movements are controlled by metabolism in a way consistent with an active extrusion. It has been shown that the Ca content of cells is intimately linked to their metabolic activities. Red cells possess a mechanism for uphill Ca extrusion which is energized by the normal metabolic processes presumably through an ATP-linked reaction. Whenever the metabolism has been reduced to a minimum, either by depletion of endogenous metabolites or by the action of inhibitors such as fluoride or iodoacetate, the Ca pump becomes inactive and a net Ca influx takes place. Tests directed to investigate the consequences of a failure in the extrusion mechanism showed that a rise in cell Ca increases Na and K permeability. K permeability being affected to a greater extent than Na. This action of internal Ca was shown to be potentiated by fluoride or iodoacetate and reversed upon addition of a supply of ATP. In the presence of inhibitors, a net Ca entry and the associated permeability change were both prevented by pyruvate or ferricyanide only under conditions which were compatible with ATP synthesis. Experiments were also done to investigate the influence of bisulphite on Na and K permeability. It was shown that bisulphite on its own only causes a small increase in permeability. Addition of Ca is required to produce a large increase in K permeability exceeding that in Na, in a way which is in accordance with a rise in cell Ca. The main conclusion is that the permeability of red cells to Na and K is regulated by the cellular metabolism through operation of a Ca pump.
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