INTERNALIZATION OF OUABAIN AND REPLACEMENT OF SODIUM PUMPS IN THE PLASMA MEMBRANES OF HeLa CELLS FOLLOWING BLOCK WITH CARDIAC GLYCOSIDES

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Abstract
The cardiac glycosides, ouabain or digoxin, when applied to HeLa cells at a concentration of 1 µM, block all Na/K pumping. The recovery of the cells from such a block involves a process of internalization of the glycoside, with its subsequent excretion and the appearance of a working Na pump at the plasma membrane. The rate of recovery of pump function probably does not depend on the direct dissociation of the glycoside from the sodium pumps on the plasma membrane. Low temperature and vinblastine slow the rate of glycoside loss from the cells (the t½ is normally about 20 h). No other agent examined altered the excretion rate. The recovery of pump function (t½ of 6 h) was reduced by all factors examined, i.e. low temperature, vinblastine, low serum concentration, cycloheximide and chloropromazine. We think this means that glycoside excretion and pump recovery are not directly related, though recovery may ultimately depend on glycoside excretion. The recovery in pump function which does occur in the absence of protein synthesis is thought to be due to a store of preformed sodium pumps held in the cell. Fresh HeLa cells ‘turnover’ their sodium pumps at a slow rate, i.e. they internalize their pumps and replace them with new ones at a rate of about 1% per hour. When pumps on the plasma membrane are blocked with cardiac glycosides, the rate of replacement can be increased by a factor of at least 4. This, therefore, constitutes a repair process. It is shown that HeLa cells provide a good model for the detoxification mechanism present in the human heart treated with therapeutic concentrations of glycosides.

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