Flux regulation of cardiac ryanodine receptor channels
Flux regulation of cardiac ryanodine receptor channels
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DOI：
10.1085/jgp.200910273
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发表时间：
2010-01-01
影响因子：
3.8
通讯作者：
Fill, Michael
中科院分区：
文献类型：
--
作者：
Liu, Yiwei;Porta, Maura;Fill, Michael
心脏2型ryanodine受体（RYR2）被Ca2+诱导的Ca2+释放（CICR）激活。CICR固有的正反馈在细胞中得到很好的控制，但这种控制的性质存在争议。在这里，我们探讨了开放的RYR2通道携带的Ca2+通量（管腔到细胞质）如何影响其自身的细胞质Ca2+调节位点以及邻近通道上的Ca2+调节位点。当存在超生理Ca2+通量（bbb3pa）时，检测到单通道的通量依赖性激活和抑制。单通道结果表明，孔抑制位点距离为1.2 +/- 0.16 nm，并且开放通道上的激活位点被屏蔽/保护，不受其自身通量的影响。我们的研究结果表明，细胞中开放的RYR2通道介导的Ca2+通量（类似于0.5 pA）太小，无法实质性地调节（激活或抑制）携带它的通道，尽管它足以激活邻近的RYR2通道。
The cardiac type 2 ryanodine receptor (RYR2) is activated by Ca2+-induced Ca2+ release (CICR). The inherent positive feedback of CICR is well controlled in cells, but the nature of this control is debated. Here, we explore how the Ca2+ flux (lumen-to-cytosol) carried by an open RYR2 channel influences its own cytosolic Ca2+ regulatory sites as well as those on a neighboring channel. Both flux-dependent activation and inhibition of single channels were detected when there were super-physiological Ca2+ fluxes (>3 pA). Single-channel results indicate a pore inhibition site distance of 1.2 +/- 0.16 nm and that the activation site on an open channel is shielded/protected from its own flux. Our results indicate that the Ca2+ flux mediated by an open RYR2 channel in cells (similar to 0.5 pA) is too small to substantially regulate (activate or inhibit) the channel carrying it, even though it is sufficient to activate a neighboring RYR2 channel.