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

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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 (IMUS) and part of the CN-induced current (ICN) with an IC50 (concentration responsible for 50 % inhibition) of 1.3 mM. The Ba2+-sensitive component was estimated to comprise 58 % of the total ICN. 3 The Ba2+-resistant component of ICN 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 ICN is due to suppression of the Na+ pump current (Ipump). 4 The non-Ipump component of ICN 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-Ipump component. 5 The I-V relationship for the non-Ipump component of ICN 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-Ipump component of ICN is due to activation of non-selective cation channels. 6 Exposure to anoxia induced a current with an amplitude comparable to that of ICN, and the anoxia-induced current apparently occluded development of ICN. 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.