Anoxia induces time‐independent K+ current through KATP channels in isolated heart cells of the guinea‐pig.

Abstract

SUMMARY1. Isolated ventricular heart cells of the guinea-pig were exposed to anoxia (Po2 < 01 Torr) which induced a time-independent K+ current. This current was studied with the patch clamp technique in the whole-cell and cell-attached configuration.2. The latency until anoxia-induced changes of whole-cell current developed was distributed exponentially (mean 10-5 min; n = 41). The current was abolished within 2-4 s of reoxygenation.

ATP‐sensitive K+ channels in heart muscle cells first open and subsequently close at maintained anoxia

“…The putative sequence of events in the cell after the onset of anoxia is: block of oxidative ATP-synthesis, inhibition of glycolysis (mechanism still un- known) leading to massive opening of the channels, further decrease of ATP thereby stopping phosphorylation by protein kinase A and closing of KATp-channels. Not clear is why the latency until the first opening of KATp-channels during anoxia is of such great variance as observed here and also in a previous report [9]. Different positions of the cells in the chamber may explain latency differences at the most in the range of a few minutes but certainly not in the range of tens of minutes.…”

“…When clamping from -80 to +40 mV under control conditions (a), the guinea pig cell showed at the beginning of the test pulse an inward Na current spike followed by some delayed rectifier current. Anoxia caused after several minutes the development of a large time-independent K + current (b) that has been described in a previous report to be carried by KATe-channels which close within a few seconds after reoxygenation [9]. Herein, the cells were not reoxygenated at the time of substantial current amplitude.…”

“…Ventricular myocytes were isolated from the mouse and guinea pig heart as described previously [9,10]. Patch clamp experiments were performed in a chamber which has been designed to establish a layer of ultra pure argon above the bath to isolate atmospheric air [11] leaving free access for the patch pipette.…”

“…One possible mechanism underlying this K ~ accumulation is the opening of ATP-sensitive K ÷ channels (KArp-channels) which has been described to appear in isolated heart cells by application of inhibitors of the oxidative metabolism [5][6][7][8] or by anoxia [9]. The most likely opening mechanism is a sufficient drop of the cytosolic ATP (or the ATP/ADP ratio).…”

Oxygen-sensitive calcium channels in vascular smooth muscle and their possible role in hypoxic arterial relaxation.

“…3 C) (8,9). Activation of KATP channels in response to hypoxia most likely requires maintained exposure to extreme low P02 (8,30).…”