Expression of the ryanodine receptor type 3 in skeletal muscle. A new partner in excitation-contraction coupling?

Mobilization of Ca2+ from the endoplasmic reticulum (ER) is mediated by two related groups of Ca2+ release channels, the inositol 1,4,5 trisphosphate (InsP3) receptors and the ryanodine receptors. The InsP3 receptors have been studied in a large number of cells where they regulate many different activities upon stimulation with a variety of agonists. Ryanodine receptors have been essentially studied with respect to their role in regulating muscle contraction in both cardiac and skeletal muscles. In the recent years, InsP3 receptors and ryanodine receptors have been found to be co-expressed in neurons and other cell types, including smooth muscle cells. This emerging picture reveals that within one cell different combinations of two or more isoforms of Ca2+ release channels (i.e., multiple InsP3 receptors and/or ryanodine receptors) can be expressed at the same time. New data on the expression of two isoforms of ryanodine receptors in developing skeletal muscles or in specialized adult muscles have provided initial ground to test the hypothesis that combinations of various Ca2+ release channels may be relevant to adapt the modality of Ca2+ release to regulation of specific cellular functions.