Functional InsP(3) receptors that may modulate excitation-contraction coupling in the heart

The roles of the Ca2+-mobilising messenger inositol 1,4,5-trisphosphate (In sP(3)) in heart are unclear, although many hormones activate InsP(3) produc tion in cardiomyocytes and some of their inotropic, chronotropic and arrhyt hmogenic effects may be due to Ca2+ release mediated by InsP(3) receptors ( InsP(3)Rs) [1-3], In the present study, we examined the expression and subc ellular localisation of InsP(3)R isoforms, and Investigated their potential role in modulating excitation-contraction coupling (EC coupling). Western, PCR and InsP(3)-binding analysis indicated that both atrial and ventricula r myocytes expressed mainly type II lnsP(3)Rs, with approximately sixfold h igher levels of InsP(3)Rs in atrial cells. Co-immunostaining of atrial myoc ytes with antibodies against type II ryanodine receptors (RyRs) and type II InsP(3)Rs revealed that the latter were arranged in the subsarcolemmal spa ce where they largely co-localised with the junctional RyRs. Stimulation of quiescent or electrically paced atrial myocytes with a membrane-permeant I nsP(3) ester, which enters cells and directly activates InsP(3)Rs, caused t he appearance of spontaneous Ca2+-release events. In addition, in paced cel ls, the InsP(3) ester evoked an increase in the amplitudes of action potent ial-evoked Ca2+ transients. These data indicate that atrial cardiomyocytes express functional InsP(3)Rs, and that these channels could modulate EC cou pling. (C) 2000 Elsevier Science Ltd. All rights reserved.