Requirement of the Inositol Trisphosphate Receptor for Activation of Store-Operated Ca <sup>2+</sup> Channels

  • Hong-Tao Ma
    Department of Biochemistry and Molecular Biology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
  • Randen L. Patterson
    Department of Biochemistry and Molecular Biology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
  • Rossum
    Department of Biochemistry and Molecular Biology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
  • Lutz Birnbaumer
    Department of Anesthesiology, University of California, Los Angeles, CA 90095, USA.
  • Katsuhiko Mikoshiba
    Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Donald L. Gill
    Department of Biochemistry and Molecular Biology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.

抄録

<jats:p> The coupling mechanism between endoplasmic reticulum (ER) calcium ion (Ca <jats:sup>2+</jats:sup> ) stores and plasma membrane (PM) store-operated channels (SOCs) is crucial to Ca <jats:sup>2+</jats:sup> signaling but has eluded detection. SOCs may be functionally related to the TRP family of receptor-operated channels. Direct comparison of endogenous SOCs with stably expressed TRP3 channels in human embryonic kidney (HEK293) cells revealed that TRP3 channels differ in being store independent. However, condensed cortical F-actin prevented activation of both SOC and TRP3 channels, which suggests that ER-PM interactions underlie coupling of both channels. A cell-permeant inhibitor of inositol trisphosphate receptor (InsP <jats:sub>3</jats:sub> R) function, 2-aminoethoxydiphenyl borate, prevented both receptor-induced TRP3 activation and store-induced SOC activation. It is concluded that InsP <jats:sub>3</jats:sub> Rs mediate both SOC and TRP channel opening and that the InsP <jats:sub>3</jats:sub> R is essential for maintaining coupling between store emptying and physiological activation of SOCs. </jats:p>

収録刊行物

  • Science

    Science 287 (5458), 1647-1651, 2000-03-03

    American Association for the Advancement of Science (AAAS)

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