Na+ pump inhibition and non‐selective cation channel activation by cyanide and anoxia in guinea‐pig chromaffin cells

Abstract

1 Hypoxia and metabolic inhibition with cyanide (CN) evoke catecholamine secretion in adrenal chromaffin cells through depolarization. We elucidated mechanisms for a CN- or anoxia-induced inward (depolarization) current, using the perforated patch method. 2 Bath application of Ba²⁺ induced a dose-dependent inhibition of a muscarine-induced current (I_MUS) and part of the CN-induced current (I_CN) with an IC₅₀ (concentration responsible for 50 % inhibition) of 1.3 mM. The Ba²⁺-sensitive component was estimated to comprise 58 % of the total I_CN. 3 The Ba²⁺-resistant component of I_CN tended to increase with shifts of membrane potential from -40 to 40 mV and was markedly suppressed by exposure to a K⁺-free solution or 200 μm ouabain, indicating that the majority of the Ba²⁺-resistant component of I_CN is due to suppression of the Na⁺ pump current (I_pump). 4 The non-I_pump component of I_CN diminished progressively in K⁺-free solution. Substitution of glucose for sucrose in a K⁺-free CN solution further diminished the CN potency to produce the non-I_pump component. 5 The I-V relationship for the non-I_pump component of I_CN had a reversal potential of -3 and -47 mV at 147 and 5.5 mM Na⁺, respectively, and showed an outward rectification, indicating that the non-I_pump component of I_CN is due to activation of non-selective cation channels. 6 Exposure to anoxia induced a current with an amplitude comparable to that of I_CN, and the anoxia-induced current apparently occluded development of I_CN. The anoxia-induced current diminished by ca 60 % in the absence of K⁺ and reversed polarity at 5 mV under K⁺-free conditions. 5 It is concluded that exposure to CN and to anoxia induces suppression of the Na⁺ pump and activation of non-selective cation channels, probably due to an ATP decrease resulting mainly from consumption by the Na⁺ pump.