TY - JOUR
T1 - Intracellular pH regulates voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells
AU - Yamakage, M.
AU - Lindeman, K. S.
AU - Hirshman, C. A.
AU - Croxton, T. L.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
KW - airway smooth muscle
KW - hypercapnia
KW - hypocapnia
KW - pig
KW - whole cell patch clamp
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U2 - 10.1152/ajplung.1995.268.4.l642
DO - 10.1152/ajplung.1995.268.4.l642
M3 - Article
C2 - 7733305
AN - SCOPUS:0029139956
SN - 1040-0605
VL - 268
SP - L642-L646
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 4 12-4
ER -