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

Curr Biol. 2000 Jul 27-Aug 10;10(15):939-42. doi: 10.1016/s0960-9822(00)00624-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Calcium Channels / metabolism*
  • Heart / physiology*
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate Receptors
  • Myocardial Contraction / physiology*
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Polymerase Chain Reaction
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Sarcoplasmic Reticulum / metabolism
  • Sarcoplasmic Reticulum / physiology

Substances

  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Receptors, Cytoplasmic and Nuclear