Effect of H⁺ on ATP-regulated K⁺ channels in feline ventricular myocytes

Using patch-clamp techniques, we examined the effects of pH on properties of ATP-regulated K⁺ channels in single myocytes isolated from cat left ventricles. ATP-K⁺ channels of inside-out patches were bilaterally exposed to 140 mM K⁺ solutions (22°C). In the absence of ATP and Mg²⁺, the channels had a linear current-voltage relationship during hyperpolarizing pulses (20-100 mV negative to the reversal potential) at both intracellular pH (pH(i)) 7.4 and 6.5, but the slope conductance was 66 ± 2 pS at pH(i) 7.4 and 46 ± 2 pS at pH(i) 6.5. Lowering pH(i) from 7.4 to 6.5 increased the mean open time (from 15.9 ± 4.6 to 35.9 ± 7.9 ms, P < 0.01) but decreased the open-state probability measured at 50 mV positive to the reversal potential (from 0.35 ± 0.04 to 0.16 ± 0.04, P < 0.01). However, in the presence of both 0.2 mM ATP and 1 mM MgCl₂, lowering pH(i) from 7.4 to 6.5 increased the mean open time (from 5.0 ± 2.6 to 17.9 ± 5.9 ms, P < 0.01) and the open-state probability (from 0.025 ± 0.010 to 0.098 ± 0.024, P < 0.01). These data indicate that increases in intracellular H⁺ concentration modulate cardiac ATP-K⁺ channel properties. Ischemia-associated decreases in pH(i) may enhance the opening of cardiac ATP-regulated K⁺ channels and resultant action potential shortening.