AJP - Cell Physiology, Vol 273, Issue 2 C520-C530, Copyright © 1997 by American Physiological Society

ARTICLES

Ca(2+)-activated Cl- currents are activated by metabolic inhibition in rat pulmonary artery smooth muscle cells

Q. Wang, Y. X. Wang, M. Yu and M. I. Kotlikoff
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6046, USA.

We report the electrophysiological and functional properties of Ca(2+)-activated Cl- currents [ICl(Ca)] in rat pulmonary artery smooth muscle and the activation of these currents by the metabolic inhibitor cyanide. Caffeine and norepinephrine (NE) evoked both Ca(2+)-activated K+ currents [IK(Ca)] and ICl(Ca) currents in voltage-clamped myocytes (-50 mV). Niflumic acid (10 microM) reduced the caffeine-induced ICl(Ca) by approximately 64% and reversibly reduced NE-induced tension. Exposure of myocytes to cyanide (2-10 mM) induced a slowly developing inward current (-50 mV) in physiological and K(+)-free solutions, which was identified as ICl(Ca) on the basis of ion selectivity and Ca2+ dependence. Cyanide elevated cytosolic Ca2+ concentration, and this elevation was markedly inhibited by preexposure to caffeine and slightly inhibited by nisoldipine. During exposure to caffeine, the Ca(2+)-activated K+ current was also augmented. Cyanide markedly prolonged ICl(Ca) activated by caffeine, increasing the half-decay time from 3.5 (control) to 29 s (cyanide); the half-decay time of the caffeine-induced IK(Ca) was not significantly affected by cyanide. The results indicate that metabolic inhibition increases [Ca2+]i and activates a prolonged, depolarizing Cl- current in pulmonary artery myocytes.

This article has been cited by other articles:

				M. Hamann, A. Gibson, N. Davies, A. Jowett, J. P. Walhin, L. Partington, K. Affleck, D. Trezise, and M. Main Human ClCa1 modulates anionic conduction of calcium-dependent chloride currents J. Physiol., May 15, 2009; 587(10): 2255 - 2274. [Abstract] [Full Text] [PDF]

				J. R. H. Mauban, C. V. Remillard, and J. X.-J. Yuan Hypoxic pulmonary vasoconstriction: role of ion channels J Appl Physiol, January 1, 2005; 98(1): 415 - 420. [Abstract] [Full Text] [PDF]

				Y.-X. Wang, Y.-M. Zheng, I. Abdullaev, and M. I. Kotlikoff Metabolic inhibition with cyanide induces calcium release in pulmonary artery myocytes and Xenopus oocytes Am J Physiol Cell Physiol, February 1, 2003; 284(2): C378 - C388. [Abstract] [Full Text] [PDF]

				I. A. Greenwood, L. J. Miller, S. Ohya, and B. Horowitz The Large Conductance Potassium Channel beta -Subunit Can Interact with and Modulate the Functional Properties of a Calcium-activated Chloride Channel, CLCA1 J. Biol. Chem., June 14, 2002; 277(25): 22119 - 22122. [Abstract] [Full Text] [PDF]

				C. M. Pabelick, G. C. Sieck, and Y. S. Prakash Signal Transduction in Smooth Muscle: Invited Review: Significance of spatial and temporal heterogeneity of calcium transients in smooth muscle J Appl Physiol, July 1, 2001; 91(1): 488 - 496. [Abstract] [Full Text] [PDF]

				Y.-X. WANG, P. K. DHULIPALA, and M. I. KOTLIKOFF Hypoxia inhibits the Na+/Ca2+ exchanger in pulmonary artery smooth muscle cells FASEB J, September 1, 2000; 14(12): 1731 - 1740. [Abstract] [Full Text]

				J. H. Jaggar, V. A. Porter, W. J. Lederer, and M. T. Nelson Calcium sparks in smooth muscle Am J Physiol Cell Physiol, February 1, 2000; 278(2): C235 - C256. [Abstract] [Full Text] [PDF]

				K. Kato, A. M. Evans, and R. Z. Kozlowski Relaxation of Endothelin-1-Induced Pulmonary Arterial Constriction by Niflumic Acid and NPPB: Mechanism(s) Independent of Chloride Channel Block J. Pharmacol. Exp. Ther., March 1, 1999; 288(3): 1242 - 1250. [Abstract] [Full Text]

				M. I. KOTLIKOFF and Y.-X. WANG Calcium Release and Calcium-Activated Chloride Channels in Airway Smooth Muscle Cells Am. J. Respir. Crit. Care Med., November 1, 1998; 158(2007): S109 - S114. [Abstract] [Full Text] [PDF]