Modulation of the Nicotinic Acetylcholine Receptor by Dioscorine in Clonal Rat Phaeochlomocytoma (PC12) Cells

Dioscorine is a toxin isolated from the tubers of tropical yam, Dioscorea hispida Schlussel that has insecticidal and antifeedant activities. The effects of dioscorine on the neuronal nicotinic acetylcholine receptor in rat clonal phaeochlomocytoma (PC12) cells were studied using whole-cell and single-channel patch clamp techniques. Dioscorine at concentrations of 0.45-450 muMM accelerated the desensitization of current induced by 100 muMM acetylcholine and suppressed the current in a dose-dependent manner. Dioscorine itself did not induce any current at concentrations ranging from 0.45 to 450 muMM. At the singlechannel level, 4.5-450 muMM dioscorine, when co-applied with 10 muMM acetylcholine, markedly shortened the open time and caused bursts to appear in a dose-dependent manner. The mean open time, mean closed time, and burst duration were decreased by dioscorine. These changes of single-channel kinetics result in a significant decrease in the total charge carried through the open channels, explaining the suppressive effect of dioscorine on acetylcholine-induced whole-cell currents. The suppressive effect of dioscorine on the acetylcholine-induced current is suggested to play an important role in the toxic actions in animals.