Regulation of the miniature plasma membrane Ca2+ channel I-min by inositol1,4,5-trisphosphate receptors

I-min is a plasma membrane-located, Ca2+-selective channel that is activate d by store depletion and regulated by inositol 1,4,5-trisphosphate (IP3). I n the present work we examined the coupling between I-min and IP3 receptors in excised plasma membrane patches from A431 cells. I-min was recorded in cell-attached mode and the patches were excised into medium containing IP3. In about 50% of experiments excision caused the loss of activation of I-mi n by IP3. In the remaining patches activation of I-min by IP3, was lost upo n extensive washes of the patch surface. The ability of IP3 to activate I-m in was restored by treating the patches with rat cerebellar microsomes reac h in IP3, receptors but not by control forebrain microsomes. The re-activat ed I-min had the same kinetic properties as I-min when it is activated by C a2+-mobilizing agonists in intact cells and by IP3 in excised plasma membra ne patches and it was inhibited by the I-crac inhibitor SKF95365. We propos e that I-min, is a form of I-crac and is gated by IP3 receptors.