INTRACELLULAR PH REGULATES VOLTAGE-DEPENDENT CA2-MUSCLE CELLS( CHANNELS IN PORCINE TRACHEAL SMOOTH)

Changes in CO2 or in pH modify airway smooth muscle contractility, To investigate the mechanisms involved, we compared K+-induced contractio ns in porcine bronchial rings exposed to different CO2 concentrations and directly measured the effects of changes in intracellular (pH(i)) or extracellular pH (pH(o)) on Ca2+ currents (I-Ca) through voltage-de pendent Ca2+ channels (VDC) in porcine tracheal smooth muscle cells. H ypocapnia and hypercapnia caused leftward and rightward shifts, respec tively, in the dose-response to K+ (P < 0.05) but did not change the m aximum force obtained. Peak I-Ca (10 mM external Ca2+) elicited by dep olarizing pulses from -80 mV was maximal [-265 +/- 12 pA (mean +/- SE) , n = 19] at + 10 mV. Intracellular acidification decreased the peak I -Ca at + 10 mV from -261 +/- 20 pA to -177 +/- 12 pA (P < 0.05, n = 4) , while intracellular alkalinization increased the peak I-Ca at + 10 m V from -302 +/- 27 pA to -368 +/- 26 pA (P < 0.05, n = 4). Changes in pH(o) had little effect on I-Ca. There was no shift in the voltage-dep endence of induced Ic, with any change. We conclude that pH(i), but no t pH(o), directly modulates the entry of Ca2+ into airway smooth muscl e cells through VDC. This mechanism may contribute to regulation of ai rway tone by CO2.