Modulation of cardiac ryanodine receptor channels by alkaline earth cations.
Modulation of cardiac ryanodine receptor channels by alkaline earth cations.
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DOI：
10.1371/journal.pone.0026693
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Copello JA
中科院分区：
文献类型：
--
作者：
Diaz-Sylvester PL;Porta M;Copello JA
心肌Ryanodine受体（RyR 2）的功能受Ca ~（2+）和Mg ~（2+）调节。为了更好地表征参与RyR 2调节的Ca 2+和Mg 2+结合位点，研究了细胞溶质和管腔碱土金属二价阳离子（M2+：Mg 2+，Ca 2+，Sr 2+，Ba 2+）对来自双层重构的猪心室的RyR 2的影响。RyR 2被M2+结合到细胞溶质通道表面的高亲和力激活位点激活，对Ca 2+或Sr 2+具有特异性。这种激活受到Mg ~（2+）和Ba ~（2+）在低亲和力M2 ~+非特异性结合位点的干扰。当测试管腔M2+作为电流载体的作用时，所有M2+增加最大RyR 2开放概率（与Cs+相比），表明在管腔表面存在低亲和力激活M2+非特异性位点。对M2+的反应因通道而异（异质性）。然而，与管腔Ba 2+或Mg 2+，RyR 2细胞质Ca 2+和咖啡因介导的激活不太敏感，开口更短，电压依赖性更显着（与RyR 2管腔Ca 2+或Sr 2+相比）。RyR 2与管腔Ba 2 +/Ca 2+的混合物和管腔加胞质Ba 2+或Mg 2+的加性作用的动力学表明管腔M2+差异作用于管腔位点，而不是通过孔进入胞质位点。这表明存在额外的管腔激活Ca 2 +/Sr 2+特异性位点，其稳定高Po模式（较少电压依赖性）并增加RyR 2对胞质Ca 2+激活的敏感性。总之，RyR 2腔和胞质表面具有至少两组M2+结合位点（对Ca 2+特异性和对Ca 2 +/Mg 2+非特异性），其动态调节通道活性和门控状态，这取决于SR电压。
Cardiac ryanodine receptor (RyR2) function is modulated by Ca2+ and Mg2+. To better characterize Ca2+ and Mg2+ binding sites involved in RyR2 regulation, the effects of cytosolic and luminal earth alkaline divalent cations (M2+: Mg2+, Ca2+, Sr2+, Ba2+) were studied on RyR2 from pig ventricle reconstituted in bilayers. RyR2 were activated by M2+ binding to high affinity activating sites at the cytosolic channel surface, specific for Ca2+ or Sr2+. This activation was interfered by Mg2+ and Ba2+ acting at low affinity M2+-unspecific binding sites. When testing the effects of luminal M2+ as current carriers, all M2+ increased maximal RyR2 open probability (compared to Cs+), suggesting the existence of low affinity activating M2+-unspecific sites at the luminal surface. Responses to M2+ vary from channel to channel (heterogeneity). However, with luminal Ba2+or Mg2+, RyR2 were less sensitive to cytosolic Ca2+ and caffeine-mediated activation, openings were shorter and voltage-dependence was more marked (compared to RyR2 with luminal Ca2+or Sr2+). Kinetics of RyR2 with mixtures of luminal Ba2+/Ca2+ and additive action of luminal plus cytosolic Ba2+ or Mg2+ suggest luminal M2+ differentially act on luminal sites rather than accessing cytosolic sites through the pore. This suggests the presence of additional luminal activating Ca2+/Sr2+-specific sites, which stabilize high Po mode (less voltage-dependent) and increase RyR2 sensitivity to cytosolic Ca2+ activation. In summary, RyR2 luminal and cytosolic surfaces have at least two sets of M2+ binding sites (specific for Ca2+ and unspecific for Ca2+/Mg2+) that dynamically modulate channel activity and gating status, depending on SR voltage.
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影响因子：
3.8
作者：
Liu, Yiwei;Porta, Maura;Fill, Michael
通讯作者：
Fill, Michael
影响因子：
3.4
作者：
Copello, JA;Barg, S;Fleischer, S
通讯作者：
Fleischer, S
影响因子：
20.1
作者：
Ching, LL;Williams, AJ;Sitsapesan, R
通讯作者：
Sitsapesan, R
影响因子：
20.1
作者：
Marx, SO;Gaburjakova, J;Marks, AR
通讯作者：
Marks, AR
DOI：
10.1016/0005-2736(90)90113-3
发表时间：
1990-02-28
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
HOLMBERG, SRM;WILLIAMS, AJ
通讯作者：
WILLIAMS, AJ