AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 4 642-L646, Copyright © 1995 by American Physiological Society
Intracellular pH regulates voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells
M. Yamakage, K. S. Lindeman, C. A. Hirshman and T. L. Croxton
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
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.
