INTRACELLULAR ACIDOSIS DIFFERENTIALLY REGULATES K-V CHANNELS IN CORONARY AND PULMONARY VASCULAR MUSCLE

Decreases in intracellular pH (pH(i)) potently dilate coronary resista nce arteries but constrict small pulmonary arteries. To define the ion ic mechanisms of these responses, this study investigated whether acut e decreases in pH(i) differentially regulate K+ currents in single vas cular smooth muscle (VSM) cells isolated from rat coronary and pulmona ry resistance arteries. In patch-clamp studies, whole cell K+ currents were elicited by 10-mV depolarizing steps between -60 and 0 mV in VSM cells obtained from 50- to 150-mu m-OD arterial branches, and pH(i) w as lowered by altering the NH4Cl gradient across the cell membrane. Pr ogressively lowering pH(i) from calculated values of 7.0 to 6.7 and 6. 4 increased the peak amplitude of K+ current in coronary VSM, cells by 15 +/- 5 and 23 +/- 3% but reduced K+ current in pulmonary VSM cells by 18 +/- 3 and 21 +/- 3%, respectively. These changes were reversed b y returning cells to the control pH(i) of 7.0 and were eliminated by d ialyzing cells with pipette solution containing 50 mmol/l HEPES to buf fer NH4Cl-induced changes in pH(i). Pharmacological block of ATP-sensi tive K+ channels and Ca2+-activated K+ channels by 1 mu mol/l glibencl amide and 100 nmol/l iberiotoxin, respectively, did not prevent change s in KC current levels induced by acidotic pH(i). However, block of vo ltage-gated K+ channels by 3 mmol/l 4-aminopyridine abolished acidosis -induced changes in K+ current amplitudes in both VSM cell types. Inte restingly, alpha-dendrotoxin (100 nmol/l), which blocks only select su btypes of voltage-gated K+ channels, abolished the acidosis-induced de crease in K+ current in pulmonary VSM cells but did not affect the aci dosis-induced increase in K+ current observed in coronary VSM cells. T hese findings suggest that opposing, tissue-specific effects of pH(i) on distinct subtypes of voltage-gated K+ channels in coronary and pulm onary VSM membranes may differentially regulate vascular reactivity in these two circulations under conditions of acidotic stress.