Intracellular pH regulates voltage-dependent Ca²⁺ channels in porcine tracheal smooth muscle cells

Changes in CO₂ or in pH modify airway smooth muscle contractility. To investigate the mechanisms involved, we compared K⁺-induced contractions 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-dependent Ca²⁺ channels (VDC) in porcine tracheal smooth muscle cells. Hypocapnia and hypercapnia caused leftward and rightward shifts, respectively, in the dose-response to K⁺ (P < 0.05) but did not change the maximum force obtained. Peak I(Ca) (10 mM external Ca²⁺) elicited by depolarizing 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 mV 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- dependence of induced I(Ca) with any change. We conclude that pH(i), but not pH(o), directly modulates the entry of Ca²⁺ into airway smooth muscle cells through VDC. This mechanism may contribute to regulation of airway tone by CO₂.