抄録
In skeletal muscle, malignant hyperthermia (MH) has been reported mainly due to increased Ca-induced Ca release (CICR) activity induced by type 1 ryanodine receptor (RyR1) mutation. There are three hot spots for mutation; the N-terminal, central and C-terminal regions. A 36 residue peptide of the central domain (DP4, Leu2442-Pro2477) activates RyR1 channel (Ikemoto & Yamamoto, 2002; Murayama et al., 2005). Recently, we also found that the weakened interdomain interaction between the N-terminal and central regions stimulates RyR1 channel activity and suggested that this abnormal channel dysfunction produces MH. On the other hand, our previous results demonstrated that RyR1 channel activity is regulated by redox states of the channel protein. Therefore, we investigated here whether RyR1 channel dysfunction induced by interdomain interaction is affected by intracellular redox states. We will show results using hydrogen peroxide, a weak oxidant for SR protein, and glutathione (GSH/GSSG) buffer on channel activity observed with or without DP4 exposure to RyR1. [J Physiol Sci. 2007;57 Suppl:S234]
