Rohani F, Frank G B
J Pharmacol Exp Ther. 1983 Feb;224(2):459-65.
When frog sartorius muscles are exposed to methadone (2-4 X 10(-4) M) the action potential recorded intracellularly is depressed and eliminated in 3 to 4 hr. This is due to a decrease in the sodium conductance as measured by the maximum rate of rise of the action potential. When the calcium 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. However, increasing the extracellular calcium to 4 mM decreased the action of methadone. As this would also increase the intracellular calcium concentration, in other experiments the free intracellular Ca+ 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 sodium conductance because the administration of caffeine by itself caused a 10% depression of the action potential maximum rate of rise and caffeine did not antagonize the action of tetrodotoxin, which is a specific sodium channel blocking agent. Finally, it was shown that the calcium ionophore, A23187, in low concentrations antagonized the depressant actions of methadone and meperidine on action potential production. It was concluded that increasing the intracellular free calcium concentration antagonized the depressant effect on excitability produced by opiate drugs acting on an intracellularly oriented opiate drug receptor.
当青蛙的缝匠肌暴露于美沙酮（2 - 4×10⁻⁴ M）时，细胞内记录的动作电位在3至4小时内受到抑制并消失。这是由于动作电位最大上升速率所测量的钠电导降低所致。当青蛙任氏液中的钙浓度（正常为1.08 mM）降至0.54 mM或升至2 mM时，美沙酮对兴奋性的影响不变。然而，将细胞外钙浓度增加到4 mM会降低美沙酮的作用。由于这也会增加细胞内钙浓度，在其他实验中，通过向任氏液中添加0.4 mM咖啡因来提高细胞内游离Ca⁺浓度。这也拮抗了美沙酮的抑制作用。咖啡因的拮抗作用并非由于咖啡因对钠电导的直接影响，因为单独给予咖啡因会使动作电位最大上升速率降低10%，且咖啡因不能拮抗河豚毒素的作用，河豚毒素是一种特异性钠通道阻断剂。最后，研究表明低浓度的钙离子载体A23187能拮抗美沙酮和哌替啶对动作电位产生的抑制作用。得出的结论是，增加细胞内游离钙浓度可拮抗阿片类药物作用于细胞内定向阿片类药物受体所产生的对兴奋性的抑制作用。
