The action of cyclic-ADP-ribose was studied on calcium release from sarcopl
asmic reticulum of skeletal muscles of neonatal and adult wild-type and RyR
3-deficient mice. cADPR increased calcium efflux from microsomes, enhanced
caffeine-induced calcium release, and, in 20% of the tests, triggered calci
um release in single muscle fibers. These responses occurred only in the di
aphragm of adult RyR3-deficient mice. cADPR action was abolished by ryanodi
ne, ruthenium red, and 8-brome-cADPM These results strongly favor a specifi
c action of cADPR on RyR1. The responsiveness of RyR1 appears in adult musc
les when RyR3 is lacking. (C) 2001 Academic Press.