Inositol trisphosphate receptor type-2: The other Ca release channel in heart

The inositol 1,4,5-trisphosphate receptor (InsP(3)R) is an intracellular calcium release channel that mediates the rise in cytosolic calcium in response to receptor-activated production of InsP(3). The predominant InsP(3)R present in acutely dissociated ventricular myocytes from rat (or ferret) hearts was the type-2 InsP(3)R. The type-2 InsP(3)Rs were isolated and reconstituted into proteoliposomes. The proteoliposomes were fused into planar lipid bilayers and the single channel behavior of the type-2 InsP(3)R defined. The permeation properties of type-1 and type-2 InsP(3)R were similar but the calcium and InsP(3) sensitivities were not. This suggests that these receptors are functionally heterogeneous. Recombinant type-1 and type-2 InsP(3)R were expressed in COS1 cells, reconstituted into proteoliposomes and fused into planar bilayers. The single channel properties of these recombinant InsP(3)Rs was reminiscent of their native counterparts. These results show that the predominant InsP(3)R in ventricular myocytes is the type-2 InsP(3)R and that the single channel properties of the type-2 InsP(3)R are distinctive. These results also set the stage for application of a mutagenesis-based experimental strategy targeted at defining the structure-functional differences between the type-1 and type-2 receptors.