pH regulation of voltage-dependent K+ channels in canine pulmonary arterial smooth muscle cells

Voltage-dependent K+ currents (K-v) may play a role in hypoxic pulmonary vase constriction. The effects of changes in extracellular pH (pH(o)) and intracellular pH (pH(i)) on K-v currents in smooth muscle cells isolated from canine pulmonary artery were studied using the amphotericin B perforated-patch technique for whole-cell recording. Under these conditions, cellular mechanisms for pH(i) regulation remain intact, and the effects of pH(o) were examined by directly changing the pH of external solutions and changes in pH(i) were produced by external application of weak extracellular acids and bases and the cation/H+ ionophore, nigericin. Ca2+-free external solutions were used to isolate whole-cell K-v currents from contaminating Ca2+-activated K+ currents. Extracellular acidification (pH(o) = 6.4-7.0) reduced K-v currents, produced a positive voltage shift in steady-state activation and reduced maximum K-v conductance (<(g)over bar (K)>). Extracellular alkalinization (pH(o) = 8.0-8.4) increased K-v currents, produced a small negative voltage shift in steady-state activation, and increased <(g)over bar (K)> Intracellular acidification produced by exposure of cells to external sodium butyrate (20 mM) or nigericin (5 mu g/ml) increased K-v currents, produced a negative voltage shift in steady-state activation, and increased <(g)over bar (K)> Intracellular alkalinization produced by exposure of cells to external trimethylamine (20 mM) reduced K-v currents, produced a small positive voltage shift in steady-state activation and reduced <(g)over bar (K)> These results suggest that the effects of pH(o) and pH(i) on K-v currents are distinctly different, but are consistent with reported effects of pH(o) and pH(i) on hypoxic pulmonary vasoconstriction, suggesting that such modulation may be mediated in part by pH-induced alterations in K-v channel activity.