DIFFERENTIAL DISTRIBUTION OF RYANODINE RECEPTOR-TYPE-3 (RYR3) GENE-PRODUCT IN MAMMALIAN SKELETAL-MUSCLES

Activation of intracellular Ca2+-release channels/ryanodine receptors (RyRs) is a fundamental step in the regulation of muscle contraction. In mammalian skeletal muscle, Ca2+-release channels containing the typ e 1 isoform of RyR (RyR1) open to release Ca2+ from the sarcoplasmic r eticulum (SR) upon stimulation by the voltage-activated dihydropyridin e receptor on the T-tubule/plasma membrane. In addition to RyR1, low l evels of the mRNA of the RyR3 isoform have been recently detected in m ammalian skeletal muscles. Here we report data on the distribution of the RyR3 gene product in mammalian skeletal muscles. Western-blot anal ysis of SR of individual muscles indicated that, at variance with the even distribution of the RyR1 isoform, the RyR3 content varies among d ifferent muscles, with relatively higher amounts being detected in dia phragm and soleus, and lower levels in abdominal muscles and tibialis anterior. In these muscles RyR3 was localized in the terminal cisterna e of the SR. No detectable levels of RyR3 were observed in the extenso r digitorum longus. Preferential high content of RyR3 in the diaphragm muscle was observed in several mammalian species. In situ hybridizati on analysis demonstrated that RyR3 transcripts are not restricted to a specific subset of skeletal-muscle fibres. Differential utilization o f the RyR3 isoform in skeletal muscle may be relevant to the modulatio n of Ca2+ release with respect to specific muscle-contraction properti es.