RyR1 exhibits lower gain of CICR activity than RyR3 in the SR: evidence for selective stabilization of RyR1 channel

Takashi Murayama, Yasuo Ogawa
2004 American Journal of Physiology - Cell Physiology  
Murayama, Takashi, and Yasuo Ogawa. RyR1 exhibits lower gain of CICR activity than RyR3 in the SR: evidence for selective stabilization of RyR1 channel. /ajpcell. 00395.2003.-We showed that frog ␣-ryanodine receptor (␣-RyR) had a lower gain of Ca 2ϩ -induced Ca 2ϩ release (CICR) activity than ␤-RyR in sarcoplasmic reticulum (SR) vesicles, indicating selective "stabilization" of the former isoform (Murayama T and Ogawa Y. J Biol Chem 276: 2953-2960. To know whether this is also the case with
more » ... alian RyR1, we determined [ 3 H]ryanodine binding of RyR1 and RyR3 in bovine diaphragm SR vesicles. The value of [ 3 H]ryanodine binding (B) was normalized by the number of maximal binding sites (B max), whereby the specific activity of each isoform was expressed. This B/B max expression demonstrated that ryanodine binding of individual channels for RyR1 was Ͻ15% that for RyR3. Responses to Ca 2ϩ , Mg 2ϩ , adenine nucleotides, and caffeine were not substantially different between in situ and purified isoforms. These results suggest that the gain of CICR activity of RyR1 is markedly lower than that of RyR3 in mammalian skeletal muscle, indicating selective stabilization of RyR1 as is true of frog ␣-RyR. The stabilization was partly eliminated by FK506 and partly by solubilization of the vesicles with CHAPS, each of which was additive to the other. In contrast, high salt, which greatly enhances [ 3 H]ryanodine binding, caused only a minor effect on the stabilization of RyR1. None of the T-tubule components, coexisting RyR3, or calmodulin was the cause. The CHAPS-sensitive intra-and intermolecular interactions that are common between mammalian and frog skeletal muscles and the isoform-specific inhibition by FKBP12, which is characteristic of mammals, are likely to be the underlying mechanisms.
doi:10.1152/ajpcell.00395.2003 pmid:14985235 fatcat:mkkhodabubaitn675da2dfaqhy