Conformational activation of Ca 2+ entry by depolarization of skeletal myotubes

Gennady Cherednichenko, Alanna M. Hurne, James D. Fessenden, Eun Hui Lee, Paul D. Allen, Kurt G. Beam, Isaac N Pessah

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Store-operated Ca 2+ entry (SOCE) occurs in diverse cell types in response to depletion of Ca 2+ within the endoplasmic/sarcoplasmic reticulum and functions both to refill these stores and to shape cytoplasmic Ca 2+ transients. Here we report that in addition to conventional SOCE, skeletal myotubes display a physiological mechanism that we term excitation-coupled Ca 2+ entry (ECCE). ECCE is rapidly initiated by membrane depolarization. Like excitation-contraction coupling, ECCE is absent in both dyspedic myotubes that lack the skeletal muscle-type ryanodine receptor 1 and dysgenic myotubes that lack the dihydropyridine receptor (DHPR), and is independent of the DHPR L-type Ca 2+ current. Unlike classic SOCE, ECCE does not depend on sarcoplasmic reticulum Ca 2+ release. Indeed, ECCE produces a large Ca 2+ entry in response to physiological stimuli that do not produce substantial store depletion and depends on interactions among three different Ca 2+ channels: the DHPR, ryanodine receptor 1, and a Ca 2+ entry channel with properties corresponding to those of store-operated Ca 2+ channels. ECCE may provide a fundamental means to rapidly maintain Ca 2+ stores and control important aspects of Ca 2+ signaling in both muscle and nonmuscle cells.

Original languageEnglish (US)
Pages (from-to)15793-15798
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number44
DOIs
StatePublished - Nov 2 2004

ASJC Scopus subject areas

  • Genetics
  • General

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