Institute of Physics, Humboldt-Universität zu Berlin, Berlin, Germany.
Biophys J. 2010 Jul 7;99(1):3-12. doi: 10.1016/j.bpj.2010.02.059.
We study Ca(2+) release through single and clustered IP(3) receptor channels on the ER membrane under presence of buffer proteins. Our computational scheme couples reaction-diffusion equations and a Markovian channel model and allows our investigating the effects of buffer proteins on local calcium concentrations and channel gating. We find transient and stationary elevations of calcium concentrations around active channels and show how they determine release amplitude. Transient calcium domains occur after closing of isolated channels and constitute an important part of the channel's feedback. They cause repeated openings (bursts) and mediate increased release due to Ca(2+) buffering by immobile proteins. Stationary domains occur during prolonged activity of clustered channels, where the spatial proximity of IP(3)Rs produces a distinct [Ca(2+)] scale (0.5-10 microM), which is smaller than channel pore concentrations (>100 microM) but larger than transient levels. While immobile buffer affects transient levels only, mobile buffers in general reduce both transient and stationary domains, giving rise to Ca(2+) evacuation and biphasic modulation of release amplitude. Our findings explain recent experiments in oocytes and provide a general framework for the understanding of calcium signals.
我们研究了在缓冲蛋白存在的情况下，内质网膜上单个和簇状 IP3 受体通道中 Ca2+ 的释放。我们的计算方案将反应扩散方程和马尔可夫通道模型耦合起来，允许我们研究缓冲蛋白对局部钙浓度和通道门控的影响。我们发现活性通道周围的钙浓度存在瞬时和稳定的升高，并展示了它们如何决定释放幅度。在孤立通道关闭后，瞬时钙域发生，并且是通道反馈的重要组成部分。它们导致重复的开放（爆发），并由于不可移动蛋白的 Ca2+ 缓冲作用而介导增加的释放。在簇状通道的长时间活动期间，会出现稳定的域，其中 IP3R 的空间接近产生明显的 [Ca2+] 标度（0.5-10 microM），其小于通道孔浓度（>100 microM）但大于瞬时水平。虽然不可移动的缓冲仅影响瞬时水平，但通常情况下，移动缓冲会降低瞬时和稳定域，导致 Ca2+ 排空和释放幅度的双相调制。我们的发现解释了最近在卵母细胞中的实验，并为理解钙信号提供了一个通用框架。
