Control of thallium and sodium fluxes in isolated adult rat heart cells by anthopleurin-A, verapamil and magnesium.

Anthopleurin-A stimulated the initial rate of 201thallium uptake by isolated adult rat heart cells by a factor of 3.41 +/- 0.56, and induced a unique pattern of spontaneous beating activity. Ouabain inhibited the basal uptake rate by 58 +/- 11% and all the anthopleurin-A stimulated rate. The Km for thallium uptake was 0.95 +/- 0.26 mM, and was not changed by anthopleurin-A. Accumulated thallium was quickly released from cells by EDTA addition. Such release was inhibited 87 +/- 10% by verapamil. Thallium reuptake was initiated by restoration of magnesium to the medium. Reuptake was mostly inhibited by ouabain, but the residual ouabain-insensitive uptake remained. The ouabain-insensitive uptake was inhibited by ATP depletion. Anthopleurin-A stimulated the rate of 22Na entry into cells by a factor of 3.17 +/- 1.65, and EDTA stimulated the rate of entry by a factor of 29.5 +/- 13.0. The EDTA-induced 22Na entry was inhibited 86 +/- 11% by verapamil. From this we draw three conclusions: The major pathway for thallium uptake is the Na-K pump. The rate of uptake by this route, like the rate of K+ uptake, is governed by the rate of cellular sodium influx; A residual ouabain-insensitive uptake route also exists which appears to require ATP but not a monovalent ion gradient; Removal of Mg and Ca induces a verapamil-sensitive monovalent channel activity which is both massive and reversible.