Evidence for sodium‐calcium exchange in the guinea‐pig ureter.

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Abstract
The effects of high-K and low-Na solutions on the smooth muscle of the guinea-pig ureter were examined in both normal tissues, and tissues in which the Na pump had been blocked by exposure to K-free solutions or ouabain (high-Na tissues). Tension recording, membrane potential measurements and ion analysis were used. High-K solutions depolarize normal tissues, leading to action potential generation and phasic contractions followed, at concentrations greater than 20-30 mM, by cessation of action potentials and the development of a biphasic contracture which declines slowly during continuous exposure. The contracture is abolished by Ca-antagonist drugs, procaine and Ca-free solutions. Short exposures of normal tissues to Na-free solutions do not result in tension development. Longer exposures may initiate tension, depending on the Na-substitute used. Sucrose causes depolarization of the cells and spike development associated with phasic contractions, superimposed on a small contracture; Li depolarizes the cells but causes no tension generation; Tris [tris(hydroxymethyl)aminomethane] hyperpolarizes the cells and a small increase in basal tone may be seen. On exposure to K-free solutions or ouabain, the tissues do not develop significant tone but their response to short application of high-K solutions grows with time. The tissues also develop the ability to contract on short applications of low-Na solutions. The low-Na contractures are resistant to concentrations of Ca antagonists that abolish the K responses of normal tissues, but are abolished in Ca-free solutions. The ability of the tissues to contract in Na-free solutions is accompanied by an increase in intracellular Na and loss of intracellular K. Even after several hours exposure to ouabain, the tissues still contain significant amounts of K and the membrane potential is the same as, or more negative than that in normal tissues. Apparently another mechanism, apart from the Na pump, can regulate intracellular Na. On continuous exposure to Na-free solutions, the contracture declines rapidly. The decline is associated with a loss of intracellular Na. The Na-free contracture is larger when K rather than Tris is used as the substitute. This difference persists in the presence of a concentration of Mn that abolishes the K contracture of normal tissues but is abolished by high concentrations (10 mM) of procaine. Neither agent greatly modifies the depolarization caused by high-K solutions or the hyperpolarization caused by Na-free (Tris). Procaine may eliminate the additional contracture associated with depolarization which is insensitive to Mn. Apparently, the tissues can maintain a low intracellular free Ca in the absence of an inwardly directed Na gradient, but that a Na-Ca exchange may play a role in determining both intracellular Na and Ca levels when the Na pump is inactivated. When intracellular Na is elevated and the Na gradient is reversed, the exchange can mediate entry of sufficient Ca to initiate a contracture.