Sodium/calcium exchange in mammalian ventricular muscle: a study with sodium-sensitive micro-electrodes

Abstract

A method for mounting and rapidly perfusing small ventricular trabeculae (diameter around 250 micron) from either ferret or guinea-pig is described. Tension, membrane potential (Em) and intracellular Na activity (aiNa) were measured. aiNa was measured using Na-sensitive micro-electrodes. At room temperature (22-26 degrees C), [Na]o 155 mmol/l and [Ca]o 5.4 mmol/l, aiNa was 10.9 mmol/l +/- S.D. 4.2 mmol/l (n = 148). When [Na]o was reduced from 155 to 1.5 mmol/l contractures developed. These were about twitch height in guinea-pig but less than the twitch height in ferret. Associated with the development of the contracture there was a decrease in aiNa. The aiNa halved within 30 s. The decrease in aiNa was not influenced by changing pHo from 7.4 to 9.5, K-free solution or strophanthidin 50 mumol/l and was not passive since, even when the [Na]o was 1.5 mmol/l, the driving force for Na ions remained inward. The aiNa decreased if [Ca]o was increased and [Na]o decreased or vice versa. On the basis of these findings it is concluded that the decrease in aiNa is mainly due to Na/Ca exchange. Despite the large decrease in aiNa the [Ca]i, as monitored by tension changes, hardly increased. Since Ca uptake does occur in Na-free conditions in heart muscle it is proposed that the mitochondria take up Ca ions and so prevent an excessive rise in cytoplasmic Ca. Strophanthidin increased both aiNa and the withdrawal contracture, but collected results from a number of experiments showed no clear correlation between the initial aiNa and contracture amplitude. Strophanthidin may, therefore, have actions additional to increasing aiNa.