ANOXIA OPENS ATP REGULATED K-CHANNELS IN ISOLATED HEART-CELLS OF THE GUINEA-PIG

We studied single channel ionic currents in cell-attached patches of guinea pig heart cells under conditions of anoxia (pO2 < 0.1 torr) to identify the type of channels which contribute to the anoxia-induced time-independent K current in whole cells. In most experiments, K currents were recorded at negative potentials as inward currents with 150 mmol/l KCl in the pipette. After periods of 5-60 minutes of anoxia. opening events of one to four voltage-independent 83 pS channels developed whose open probability reached a steady state value between 0.6 and 0.95 (T = 35-degrees-C). The reversal potential of the unitary currents, determined at 150 mmol/l and 10.8 mmol/l K+ in the pipette, showed that the channels were highly selective for K+ ions. Open time histograms were fitted by two or three exponentials of which the fast time constant (tau-o1 = 0.46 +/- 0.20 ms, mean +/- SD) was bandwidth-limited by our filter and the slow components substantially varied (tau-o2 = 1.5-19 ms; tau-o3 = 23-200 ms). Voltage ramp experiments showed that the channels were slightly rectifying in an inward direction. The unitary conductance of anoxia-induced outward currents at reduced K+ in the pipette was smaller (11 pS at 5.4 mmol K+, 25 pS at 10.8 mmol/l K+) than in excised patches. It is concluded that in isolated cardiocytes substrate-free anoxia causes opening of ATP regulated K channels whose conductance is reduced at physiological levels of [K+]o by a fast block, most likely by intracellular Mg++ and Na+.