Liu Yiwei, Porta Maura, Qin Jia, Ramos Jorge, Nani Alma, Shannon Thomas R, Fill Michael
Department of Molecular Physiology and Biophysics, Rush University Medical Center, Chicago, IL 60612, USA.
J Gen Physiol. 2010 Jan;135(1):15-27. doi: 10.1085/jgp.200910273. Epub 2009 Dec 14.
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 (approximately 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.
心脏2型兰尼碱受体（RYR2）由钙诱导的钙释放（CICR）激活。CICR固有的正反馈在细胞中受到良好控制，但其控制本质存在争议。在此，我们探究开放的RYR2通道所携带的Ca2+通量（从内质网腔到细胞质）如何影响其自身的细胞质Ca2+调节位点以及相邻通道上的调节位点。当存在超生理Ca2+通量（>3 pA）时，检测到了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，且开放通道上的激活位点受到其自身通量的屏蔽/保护。我们的结果表明，细胞中开放的RYR2通道介导的Ca2+通量（约0.5 pA）太小，不足以显著调节（激活或抑制）携带该通量的通道，尽管它足以激活相邻的RYR2通道。
