HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 52, 37471-37478, December 28, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/52/37471    most recent M701379200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, T. Articles by Lopez, J. R. Search for Related Content PubMed PubMed Citation Articles by Yang, T. Articles by Lopez, J. R. Social Bookmarking                      What's this?

Enhanced Excitation-coupled Calcium Entry in Myotubes Is Associated with Expression of RyR1 Malignant Hyperthermia Mutations^*

Tianzhong Yang, Paul D. Allen¹, Isaac N. Pessah, and Jose R. Lopez^¶

From the Department of Anesthesiology Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, the Department of Molecular Biosciences, School of Veterinary Medicine, University of California at Davis, Davis, California, 95606, and the ^¶Centro de Biofisica y Bioquimica, Instituto Venezolano de Investigaciones Cientificas, Caracas Apartado 21827, Venezuela

Myotubes expressing wild type RyR1 (WT) or RyR1 with one of three malignant hyperthermia mutations R615C, R2163C, and T4826I (MH) were exposed sequentially to 60 mM KCl in Ca²⁺-replete and Ca²⁺-free external buffers (Ca+ and Ca–, respectively) with 3 min of rest between exposures. Although the maximal peak amplitude of the Ca²⁺ transients during K⁺ depolarization was similar for WT and MH in both external buffers, the rate of decay of the sustained phase of the transient during K⁺ depolarization (decay rate) in Ca+ was 50% slower for MH. This difference was eliminated in Ca–, and the relative decay rates were faster for both genotypes than in Ca+. The integrated Ca²⁺ transient in Ca–compared with Ca+ was reduced by 50–60% for MH and 20% for WT. The decay rate was not affected by [K⁺] x [Cl^–] product or NiCl₂ (2 mM) supplementation of Ca–. The addition of La²⁺ (0.1 mM), or SKF 96365 (20 µM) to Ca+ significantly accelerated decay rates for both WT and MH, but their effect was significantly greater in MH. Nifedipine (1 µM) had no effect, suggesting that the mechanism for this difference was not a reduction in L-type Ca²⁺ channel Ca²⁺ current. These data strongly suggest: 1) the decay rate in skeletal myotubes is related in part to Ca²⁺ entry through the ECCE channel; 2) the MH mutations enhance ECCE compared with wild type; and 3) the increased Ca²⁺ entry might play a significant role in the pathophysiology of MH.

Received for publication, February 16, 2007 , and in revised form, September 12, 2007.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Anesthesiology Perioperative and Pain Medicine, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115. E-mail: pdallen{at}partners.org.

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

This article has been cited by other articles:

				R. T. Dirksen Checking your SOCCs and feet: the molecular mechanisms of Ca2+ entry in skeletal muscle J. Physiol., July 1, 2009; 587(13): 3139 - 3147. [Abstract] [Full Text] [PDF]

				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]

				A. D. Lyfenko and R. T. Dirksen Differential dependence of store-operated and excitation-coupled Ca2+ entry in skeletal muscle on STIM1 and Orai1 J. Physiol., October 15, 2008; 586(20): 4815 - 4824. [Abstract] [Full Text] [PDF]