AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 6 776-L782, Copyright © 1995 by American Physiological Society

ARTICLES

Cholinergic regulation of voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells

M. Yamakage, C. A. Hirshman and T. L. Croxton
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.

To investigate cholinergic regulation of voltage-dependent Ca2+ channels (VDCs) in airway smooth muscle, we measured inward currents through VDCs in enzymatically dispersed porcine tracheal smooth muscle cells using conventional (10 mM Ca2+ as charge carrier) and nystatin-perforated (5 mM Ba2+ as charge carrier) whole cell patch clamp techniques. Carbachol (CCh) had significant and dose-dependent inhibitory effects on inward currents (12% with 10(-7) M and 42% with 10(-6) M) in perforated whole cell clamp experiments, but had no effect on currents in conventional whole cell experiments. CCh also shifted the steady-state inactivation curve to more negative potentials. Further experiments tested the hypothesis that CCh inhibits VDCs in part by the activation of protein kinase C (PKC). Phorbol 12,13-diacetate, an exogenous PKC activator, inhibited currents through VDCs. and calphostin C, a specific PKC inhibitor, antagonized the inhibitory effect of CCh. Furthermore, intracellular exposure to the activating PKC fragment 530-558, using a pipette perfusion technique, also inhibited currents through VDCs. We conclude that cholinergic receptor stimulation can inhibit inward Ca2+ currents through VDCs of porcine tracheal smooth muscle and that this effect may be mediated in part by activation of PKC.

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