Ikemoto T, Takeshima H, Iino M, Endo M
Department of Pharmacology, Saitama Medical School, Moroyama-machi, Saitama 350-0495, Japan.
Pflugers Arch. 1998 Dec;437(1):43-8. doi: 10.1007/s004240050744.
We analyzed the effects of calmodulin (CaM) on Ca2+-induced Ca2+ release (CICR) in mouse skeletal muscle cells expressing only ryanodine receptor type 1 (RyR-1) or type 3 (RyR-3) following targeted disruption of one of the RyR genes. Under Mg2+-free conditions, CaM potentiated CICR via RyR-3 at low Ca2+ concentrations (pCa>/=6) but inhibited CICR at high Ca2+ concentrations (pCa</=5). On the other hand, CaM potentiated CICR via RyR-1 between pCa 7 and pCa 5. Greater concentrations of CaM were required for potentiation of CICR at pCa 6 than for the inhibition at pCa 5 in the RyR-3-expressing cells. Similarly, higher concentrations of CaM were required for the potentiation of CICR via RyR-1 at pCa 6 than potentiation at pCa 5. In the presence of Mg2+ and beta,gamma-methyleneadenosine 5'-trisphosphate (AMPOPCP), the same differential effects of CaM on the CICR via the different subtypes of RyR were observed. These data suggest that multiple CaM-binding sites are involved in the differential effects on RyR-1 and RyR-3. These effects of CaM are important for the evaluation of the physiological roles of RyRs.
在敲除其中一个兰尼碱受体（RyR）基因后，我们分析了钙调蛋白（CaM）对仅表达1型（RyR-1）或3型（RyR-3）兰尼碱受体的小鼠骨骼肌细胞中Ca2+诱导的Ca2+释放（CICR）的影响。在无Mg2+条件下，在低Ca2+浓度（pCa≥6）时，CaM通过RyR-3增强CICR，但在高Ca2+浓度（pCa≤5）时抑制CICR。另一方面，在pCa 7至pCa 5之间，CaM通过RyR-1增强CICR。在表达RyR-3的细胞中，pCa 6时增强CICR所需的CaM浓度高于pCa 5时抑制所需的浓度。同样，pCa 6时通过RyR-1增强CICR所需的CaM浓度高于pCa 5时增强所需的浓度。在存在Mg2+和β,γ-亚甲基腺苷5'-三磷酸（AMPOPCP）的情况下，观察到CaM对通过不同亚型RyR的CICR具有相同的差异效应。这些数据表明，多个CaM结合位点参与了对RyR-1和RyR-3的差异效应。CaM的这些效应对于评估RyRs的生理作用很重要。
