PLASMA-MEMBRANE HYPERPOLARIZATION BY CYANIDE IN CHROMAFFIN CELLS - ROLE OF POTASSIUM CHANNELS

Exposure of rat pheochromocytoma (PC12) cells to cyanide produces elev ation of cytosolic calcium, impaired Na+-H+ exchange, membrane lipid p eroxidation and release of neurotransmitters. Since these observations suggested cyanide alters plasma membrane function, the present study examined the effect of NaCN on the membrane potential of undifferentia ted PC12 cells in suspension. In PC12 cells loaded with the voltage se nsitive fluorescent dye, bis-oxonol, cyanide (2.5-10 mM) elicited an i mmediate (within seconds), concentration related decrease in fluoresce nce, indicating hyperpolarization of the plasma membrane. Increasing e xtracellular K+ concentra tion to 20 mM blocked the effect of cyanide (5 mM), suggesting cyanide increased K+ efflux. Pretreatment with quin ine blocked the cyanide-induced hyperpolarization, whereas glyburide h ad little effect, showing the hyperpolarization produced by cyanide wa s due to activation of Ca2+ sensitive K+ channels. Removal of Ca2+ fro m the media did not influence cyanide-induced hyperpolarization. Howev er, buffering intracellular Ca2+ by loading cells with the Ca2+ chelat ors, Quin II or BAPTA, abolished the cyanide effect, showing cytosolic Ca2+ is a key factor. These findings suggest that cyanide mobilizes C a2+ from intracellular stores which leads to hyperpolarization via the activation of Ca2+ sensitive K+ channels.