Type 3 and type 1 ryanodine receptors are localized in triads of the same mammalian skeletal muscle fibers

The type 3 ryanodine receptor (RyR3) is a ubiquitous calcium release channe l that has recently been found in mammalian skeletal muscles. However, in c ontrast to the skeletal muscle isoform (RyR1), neither the subcellular dist ribution nor the physiological role of RyR3 are known. Here, we used isofor m-specific antibodies to localize RyR3 in muscles of normal and RyR knockou t mice. In normal hind limb and diaphragm muscles of young mice, RyR3 was e xpressed in all fibers where it was codistributed with RyR1 and with the sk eletal muscle dihydropyridine receptor. This distribution pattern indicates that RyR3 is localized in the triadic junctions between the transverse tub ules and the sarcoplasmic reticulum. During development, RyR3 expression de clined rapidly in some fibers whereas other fibers maintained expression of RyR3 into adulthood. Comparing the distribution of RyR3-containing fibers with that of known fiber types did not show a direct correlation. Targeted deletion of the RyR1 or RyR3 gene resulted in the expected loss of the targ eted isoform, but had no adverse effects on the expression and localization of the respective other RyR isoform, The localization of RyR3 in skeletal muscle triads, together with RyR1, is consistent with an accessory function of RyR3 in skeletal muscle excitation-contraction coupling.