Functional InsP3 receptors that may modulate excitation-contraction coupling in the heart

Peter Lipp, Mika Laine, Stephen C. Tovey, Kylie M. Burrell, Michael J. Berridge, Wenhong Li, Martin D. Bootman

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180 Scopus citations

Abstract

The roles of the Ca2+-mobilising messenger inositol 1,4,5-trisphosphate (InsP3) in heart are unclear, although many hormones activate InsP3 production in cardiomyocytes and some of their inotropic, chronotropic and arrhythmogenic effects may be due to Ca2+ release mediated by InsP3 receptors (InsP3Rs) [1-3]. In the present study, we examined the expression and subcellular localisation of InsP3R isoforms, and investigated their potential role in modulating excitation-contraction coupling (EC coupling). Western, PCR and InsP3-binding analysis indicated that both atrial and ventricular myocytes expressed mainly type II InsP3Rs, with approximately sixfold higher levels of InsP3Rs in atrial cells. Co-immunostaining of atrial myocytes with antibodies against type II ryanodine receptors (RyRs) and type II InsP3Rs revealed that the latter were arranged in the subsarcolemmal space where they largely co-localised with the junctional RyRs. Stimulation of quiescent or electrically paced atrial myocytes with a membrane-permeant InsP3 ester, which enters cells and directly activates InsP3Rs, caused the appearance of spontaneous Ca2+-release events. In addition, in paced cells, the InsP3 ester evoked an increase in the amplitudes of action potential-evoked Ca2+ transients. These data indicate that atrial cardiomyocytes express functional InsP3Rs, and that these channels could modulate EC coupling.

Original languageEnglish (US)
Pages (from-to)939-942
Number of pages4
JournalCurrent Biology
Volume10
Issue number15
DOIs
Publication statusPublished - Aug 1 2000

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Lipp, P., Laine, M., Tovey, S. C., Burrell, K. M., Berridge, M. J., Li, W., & Bootman, M. D. (2000). Functional InsP3 receptors that may modulate excitation-contraction coupling in the heart. Current Biology, 10(15), 939-942. https://doi.org/10.1016/S0960-9822(00)00624-2