title: Intracellular pH regulates voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells.
abstract: 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 (pHi) or extracellular pH (pHo) on Ca2+ currents (ICa) 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 ICa (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 ICa at +10 mV from -261 +/- 20 pA to -177 +/- 12 pA (P < 0.05, n = 4), while intracellular alkalinization increased the peak ICa at +10 mV from -302 +/- 27 pA to -368 +/- 26 pA (P < 0.05, n = 4). Changes in pHo had little effect on ICa. There was no shift in the voltage-dependence of induced ICa with any change. We conclude that pHi, but not pHo, directly modulates the entry of Ca2+ into airway smooth muscle cells through VDC. This mechanism may contribute to regulation of airway tone by CO2.
authors.affiliation: Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
authors.forename: M
authors.initials: M
authors.lastname: Yamakage
authors.forename: K S
authors.initials: KS
authors.lastname: Lindeman
authors.forename: C A
authors.initials: CA
authors.lastname: Hirshman
authors.forename: T L
authors.initials: TL
authors.lastname: Croxton
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D002245:Carbon Dioxide / Q000378:metabolism; D004553:Electric Conductivity; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D013552:Swine; D014132:Trachea / Q000166:cytology / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D002245:Carbon Dioxide; D011188:Potassium