Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 296K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wilkens, C. M. Articles by Beam, K. G. Search for Related Content PubMed PubMed Citation Articles by Wilkens, C. M. Articles by Beam, K. G. Social Bookmarking                            What's this?

Original Article

Potentiation of the Cardiac L-Type Ca²⁺ Channel (_1C) by Dihydropyridine Agonist and Strong Depolarization Occur via Distinct Mechanisms

^a Department of Anatomy and Neurobiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523
^b Department of Biochemical Pharmacology, University of Innsbruck, A-6020 Innsbruck, Austria
Department of Anatomy and Neurobiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.(970) 491-7907

kbeam{at}lamar.colostate.edu

A defining property of L-type Ca²⁺ channels is their potentiation by both 1,4-dihydropyridine agonists and strong depolarization. In contrast, non–L-type channels are potentiated by neither agonist nor depolarization, suggesting that these two processes may by linked. In this study, we have tested whether the mechanisms of agonist- and depolarization-induced potentiation in the cardiac L-type channel (_1C) are linked. We found that the mutant L-type channel GFP-_1C(TQYM), bearing the mutations T1066Y and Q1070M, was able to undergo depolarization-induced potentiation but not potentiation by agonist. Conversely, the chimeric channel GFP-CACC was potentiated by agonist but not by strong depolarization. These data indicate that the mechanisms of agonist- and depolarization-induced potentiation of _1C are distinct. Since neither GFP-CACC nor GFP-CCAA was potentiated significantly by depolarization, no single repeat of _1C appears to be responsible for depolarization-induced potentiation. Surprisingly, GFP-CACC displayed a low estimated open probability similar to that of the _1C, but could not support depolarization-induced potentiation, demonstrating that a relatively low open probability alone is not sufficient for depolarization-induced potentiation to occur. Thus, depolarization-induced potentiation may be a global channel property requiring participation from all four homologous repeats.

Key Words: ion channel modulation • facilitation • muscle

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				R. A. Bannister, I. N. Pessah, and K. G. Beam The Skeletal L-type Ca2+ Current Is a Major Contributor to Excitation-coupled Ca2+ entry J. Gen. Physiol., December 29, 2008; 133(1): 79 - 91. [Abstract] [Full Text] [PDF]

				R. A. Bannister, M. Grabner, and K. G. Beam The {alpha}1S III-IV Loop Influences 1,4-Dihydropyridine Receptor Gating but Is Not Directly Involved in Excitation-Contraction Coupling Interactions with the Type 1 Ryanodine Receptor J. Biol. Chem., August 22, 2008; 283(34): 23217 - 23223. [Abstract] [Full Text] [PDF]

				S. J. Tavalin, D. Shepherd, R. K. Cloues, S. E. H. Bowden, and N. V. Marrion Modulation of Single Channels Underlying Hippocampal L-Type Current Enhancement by Agonists Depends on the Permeant Ion J Neurophysiol, August 1, 2004; 92(2): 824 - 837. [Abstract] [Full Text] [PDF]

				V. Leuranguer, R. T. Dirksen, and K. G. Beam Potentiated L-type Ca2+ Channels Rectify J. Gen. Physiol., May 27, 2003; 121(6): 541 - 550. [Abstract] [Full Text] [PDF]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents