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

Lipp, Peter; Laine, Mika; Tovey, Stephen C.; Burrell, Kylie M.; Berridge, Michael J.; Li, Wenhong and Bootman, Martin D. (2000). Functional InsP₃ receptors that may modulate excitation-contraction coupling in the heart. Current biology, 10(15) pp. 939–942.

DOI: https://doi.org/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.

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