Intracellular protons inhibit inward rectifier K+ channel of guinea-pig ventricular cell membrane

The effect of intracellular protons (H_i⁺) on the inward rectifier K⁺ channel of the guinea-pig ventricular cell membrane was examined, using the patch-clamp technique. The inward single-channel current was recorded in inside-out and outside-out patch configurations, while the pH of the solution perfusing the intra and extracellular side, respectively, was varied. Low intracellular pH (pH_i), but not low extracellular pH, inhibited the channel. Low pH_i reduced the unit amplitude, which was about 20% smaller at pH_i 6.0 than that at pH_i 7.4 at every voltage tested. The slope conductance decreased from 41.7 pS at pH_i 7.4 to 35.1 pS at pH_i 6.0. Low pH_i also reduced the channel activity without apparent voltage dependence. The concentration/response curve indicated the half-maximum inhibition at pH_i 6.11 and a Hill coefficient of 2.52. Lowering the pH_i from 7.4 to 6.0 did not affect the distributions of the open times and the closed times below 50 ms, while the time constant of the histogram constructed from closings longer than 50 ms was approximately doubled. These results indicate that the inward rectifier K⁺ channel in ventricular myocytes is inhibited by H⁺ from the intracellular side. This might contribute to the depolarization of the resting membrane potential induced by intracellular acidosis during myocardial ischaemia.