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This Article Full Text Full Text (PDF) All Versions of this Article: 289/6/G998    most recent 00529.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Kovac, J. R. Articles by Sims, S. M. Search for Related Content PubMed PubMed Citation Articles by Kovac, J. R. Articles by Sims, S. M.

NEUROREGULATION AND MOTILITY

Functional and molecular analysis of L-type calcium channels in human esophagus and lower esophageal sphincter smooth muscle

Departments of ¹Physiology and Pharmacology and ²Medicine, The University of Western Ontario, London, Ontario, Canada

Submitted 30 November 2004 ; accepted in final form 12 July 2005

Excitation of human esophageal smooth muscle involves the release of Ca²⁺ from intracellular stores and influx. The lower esophageal sphincter (LES) shows the distinctive property of tonic contraction; however, the mechanisms by which this is maintained are incompletely understood. We examined Ca²⁺ channels in human esophageal muscle and investigated their contribution to LES tone. Functional effects were examined with tension recordings, currents were recorded with patch-clamp electrophysiology, channel expression was explored by RT-PCR, and intracellular Ca²⁺ concentration was monitored by fura-2 fluorescence. LES muscle strips developed tone that was abolished by the removal of extracellular Ca²⁺ and reduced by the application of the L-type Ca²⁺ channel blocker nifedipine (to 13 ± 6% of control) but was unaffected by the inhibition of sarco(endo)plasmic reticulum Ca²⁺-ATPase by cyclopiazonic acid (CPA). Carbachol increased tension above basal tone, and this effect was attenuated by treatment with CPA and nifedipine. Voltage-dependent inward currents were studied using patch-clamp techniques and dissociated cells. Similar inward currents were observed in esophageal body (EB) and LES smooth muscle cells. The inward currents in both tissues were blocked by nifedipine, enhanced by Bay K8644, and transiently suppressed by acetylcholine. The molecular form of the Ca²⁺ channel was explored using RT-PCR, and similar splice variant combinations of the pore-forming _1C-subunit were identified in EB and LES. This is the first characterization of Ca²⁺ channels in human esophageal smooth muscle, and we establish that L-type Ca²⁺ channels play a critical role in maintaining LES tone.

patch clamp; Ca²⁺ current; muscle tone; polymerase chain reaction; Ca_v1.2

This article has been cited by other articles:

				S. M. Sims, T. Chrones, and H. G. Preiksaitis Calcium Sensitization in Human Esophageal Muscle: Role for RhoA Kinase in Maintenance of Lower Esophageal Sphincter Tone J. Pharmacol. Exp. Ther., October 1, 2008; 327(1): 178 - 186. [Abstract] [Full Text] [PDF]

				J. R. Kovac, T. Chrones, and S. M. Sims Temporal and spatial dynamics underlying capacitative calcium entry in human colonic smooth muscle Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G88 - G98. [Abstract] [Full Text] [PDF]