CALCIUM ANTAGONISM OF AN OPIATE DRUG EFFECT ON AN EXCITABLE CELL-MEMBRANE

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Abstract
When frog sartorius muscles are exposed to methadone (2-4 .times. 10-4 M) the action potential recorded intracellularly is depressed and eliminated in 3-4 h. This is due to a decrease in the Na conductance as measured by the Vmax rate of rise of the action potential. When the Ca concentration in frog Ringer''s solution (normally 1.08 mM) was either lowered to 0.54 mM or raised to 2 mM, the effect of methadone on excitability was unchanged. Increasing the extracellular Ca to 4 mM decreased the action of methadone. As this would also increase the intracellular Ca concentration, in other experiments the free intracellular Ca2+ concentration was raised by adding 0.4 mM caffeine to the Ringer''s solution. This also antagonized the depressant action of methadone. The antagonistic action of caffeine was not due to a direct effect of caffeine on Na conductance, because the administration of caffeine by itself caused a 10% depression of the action potential Vmax of rise and caffeine did not antagonize the action of tetrodotoxin, which is a specific Na channel blocking agent. The calcium ionophore, A23187 [calcimycin] in low concentrations antagonized the depressant actions of methadone and meperidine on action potential production. Increasing the intracellular free Ca concentration evidently antagonized the depressant effect on excitability produced by opiate drugs acting on an intracellularly oriented opiate drug receptor.

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