Evidence for a direct action of X-537 A on the cardiac plasma membrane as an ionophore.

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In some cardiac muscles made inexcitable by inactivating the fast sodium channels with elevated potassium, it has been shown that several agents, including catecholamines, induce slow electrical responses with concomitant contractions. The response is considered to be carried through the slow Ca2+ or Ca2+-Na+ channels on the basis of several types of experimental evidence. X-537A produced this type of electrical and mechanical responses in papillary muscles from both normal and reserpinized guinea pigs. A beta-adrenergic blocking agent, sotalol, did not modify this X-537A-induced responses. Tyramine, an agent known to release endogenous catecholamines, produced the same mechanical responses in normal papillary muscles, but it did not in those from the reserpinized animals. Therefore, it can be concluded that X-537A does act, at least at relatively high concentrations, on the cardiac plasma membrane to increase the Ca2+ permeability, which can be visualized with the aid of the specially designed experiments as described above.

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