Anoxia opens ATP regulated K channels in isolated heart cells of the guinea pig

Abstract

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°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 (τ_o1=0.46±0.20 ms, mean±SD) was bandwidth-limited by our filter and the slow components substantially varied (τ_o2=1.5–19 ms: τ_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⁺.