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Cat adrenal gland was perfused retrogradely with modified Locke's medium and we investigated the effect of divalent cations on catecholamine release in response to KCl depolarization and to substitution of sucrose for NaCl in order to study the role of surface potential in the gating mechanism of Ca channels. The response to 20 mM KCl was largest at 10 mM Sr and it was less at 20 and 40 mM. Inhibition by the higher concentration of Sr was weakened by the addition of 10 mM Mg to the medium or by raising the concentration of KCl. The response to 30 mM KCl at 10 mM Sr was much larger than that at 10 mM Ca, and it was reduced by the addition of Ca. Stronger depolarization tended to reduce the difference between Ca and Sr in supporting secretion. The addition of 10 mM Sr increased the response to 30 mM KCl in the presence of 0.1 or 0.5 mM Ca, but tended to reduce the response in the presence of 2 or 10 mM Ca. Response to sucrose substitution was also reduced by increasing the concentration of Ca or Sr. Inhibition by Ca was counteracted by raising the concentration of K, Rb, or Cs so that the concentration of Ca producing the maximum response tended to be higher. Similarly, inhibition by Sr was partially reversed by raising the KCl concentration to 15 mM. These results are in accord with the idea that a high concentration of permeant divalent cations reduces the number of activated Ca channels by decreasing the surface potential, and also that Ca is more effective than Sr in decreasing the surface potential by binding to the surface negative charges. Increase of catecholamine secretion by a novel dihydropyridine BAY K 8644 was greater in the presence of Sr than with Ca.

Possible role of surface potential in the gating mechanism of Ca channels concerned with catecholamine secretion in the adrenal.