Effects of ischaemia, reperfusion and α1-adrenergic receptor stimulation on the inositoltrisphosphate receptor population in rat heart atria and ventricles

Huisamen B. ; Mouton R. ; Opie L.H. ; Lochner A. (1994)


Binding sites specific for inositol 1,4,5-trisphosphate (InsP3) have been demonstrated in sarcoplasmic reticulum vesicles isolated from heart muscle. Scatchard analysis of a binding isotherm indicated a high as well as a low affinity binding site [1]. In this study a comparison was made between InsP3 binding to crude microsomal membranes prepared from rat heart atria and ventricles respectively. Results obtained showed a four-fold higher incidence of binding to atrial membranes. Furthermore, the receptor populations of the atria and ventricles behaved differently during conditions causing fluctuations in tissue InsP3 levels, viz. ischaemia, reperfusion and α1- adrenergic stimulation. Reperfusion, as well as phenylephrine stimulation, caused an increase in InsP3 levels associated with down-regulation of the ventricular InsP3 receptor population while binding to atrial binding sites was elevated. In the ventricular population this down-regulation was the result of a reduction in B(max) alone with no changes in the Kd values of the high- or the low-affinity binding sites. The reason(s) for the differential response of the atrial and ventricular InsP3 receptor populations to changes in InsP3 levels, remains to be established.

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