Characterization of the calcium-release channel/ryanodine receptor from zebrafish skeletal muscle

Calcium (Ca2+)-mediated signaling is fueled by two sources for Ca2+:Ca2+ ca n enter through Ca2+-channels located in the plasma membrane and can also b e released from intracellular stores. In the present study the intracellula r Ca2+ release channel/ryanodine receptor (RyR) from zebrafish skeletal mus cle was characterized. Two RyR isoforms could be identified using immunoblo tting and single-channel recordings. Biophysical properties as well as the regulation by modulators of RyR, ryanodine, ruthenium red and caffeine, wer e measured. Comparison with other RyRs showed that the zebrafish RyRs have features observed with all RyRs described to date and thus, can serve as a model system in future genetic and physiological studies. However, some dif ferences in the biophysical properties were observed. The slope conductance for both isoforms was higher than that of the mammalian RyR type 1 (RyR1) measured with divalent ions. Also, inhibition by millimolar Ca2+ concentrat ions of the RyR isoform that is inhibited by high Ca2+ concentrations (tele ost a RyR isoform) was attenuated when compared to mammalian RyRs. Due to t he widespread expression of RyR these findings have important implications for the interpretation of the role of the RyR in Ca2+ signaling when compar ing zebrafish with mammalian physiology, especially when analyzing mutation s underlying physiological changes in zebrafish.