The heart is a heterogeneous tissue composed of several cell types tailored for specialized functions. We found that intracellular channels also exhibit regional specialization. In cardiac and skeletal muscle these channels are called the calcium-release channel and are identified by activation with either calcium or caffeine and inhibition by the hexavalent cation ruthenium red. The calcium-release channel of the sarcoplasmic reticulum from the interventricular septum has a smaller conductance (31 pS vs. 100 pS) and has longer open and closed times when compared with the channel from left-ventricular free wall. An additional calcium-permeable channel with an even smaller conductance (17 pS) was found in the septum, and this channel is similar to the inositol 1,4,5-trisphosphate-gated channel from smooth muscle and different from the calcium-release channel (ryanodine receptor) from skeletal and cardiac muscle. The inositol 1,4,5-trisphosphate-activated channel may be derived from specialized conducting tissue that is relatively abundant in the septum, whereas the other calcium-release channels may be derived from regionally specialized myocardial cells in the septum and free wall.