Gramicidin toxicity in NG108-15 cells: protective effects of acetamidine and guanidine.

J A Doebler

Index: Cell Biol. Toxicol. 15(5) , 279-89, (1999)

Full Text: HTML

Abstract

Studies were conducted using a novel in vitro approach to investigate the efficacy of acetamidine hydrochloride (ACE) and guanidine hydrochloride (GUAN), previously shown to block gramicidin D (GRAM) channels in artificial membranes, in preventing the toxic effects of GRAM in NG108-15 (neuroblastoma x glioma hybrid) cells. Specifically, intracellular microelectrode techniques were employed to examine changes in membrane resting potential (Vm) and input resistance (Rin). At 1 micromol/L, ACE significantly reduced loss of Vm induced by 1 or 10 microg/ml GRAM, although higher concentrations of ACE did not afford enhanced antagonism. GUAN, in contrast, produced a concentration-dependent antagonism of GRAM-induced Vm and Rin loss, with high concentrations (10 or 100 micromol/L) completely preventing diminutions in both Vm and Rin. In control cells superfused without GRAM, ACE produced a direct, concentration-dependent reduction in Vm and Rin, whereas GUAN hyperpolarized NG108-15 cells but did not alter Rin. These data represent the initial demonstration of the reversal of GRAM toxicity in an intact cell system.