Stochastic amplification of calcium-activated potassium currents in Ca2+ microdomains
Stochastic amplification of calcium-activated potassium currents in Ca2+ microdomains
复制标题
Ca2 微区中钙激活钾电流的随机放大
DOI：
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发表时间：
2011
影响因子：
1.2
通讯作者：
W. Ditto
中科院分区：
文献类型：
--
作者：
D. A. Stanley;B. Bardakjian;M. Spano;W. Ditto
小电导（SK）钙活化钾通道存在于全身的许多组织中，并随着细胞内钙水平的升高而开放。在海马神经元中，SK通道与l型钙通道在空间上共定位。由于钙瞬态进入微畴的限制，只有有限数量的l型Ca2+通道可以激活SK，因此，随机门控变得相关。使用钙微域的随机模型，我们预测由Ca2+通道门控引起的细胞内Ca2+波动可以将SK2阈下活性提高1-2个数量级。这有效地降低了希尔系数的值。为了解释潜在的机制，我们展示了与钙通道随机门控相关的短、高振幅钙脉冲如何比确定性模拟产生的稳定钙信号更有效地激活SK2通道。这种随机放大是由两个因素造成的：第一，低钙水平下SK2通道稳态激活曲线的超线性上升；第二，钙脉冲期间通道时间常数的瞬间降低，导致通道接近稳态激活值的速度远远快于其衰减。随机放大可以潜在地解释阈下和阈上机制的统一模型中SK2的激活。此外，我们预计这是一种普遍现象，与许多蛋白质被随机配体释放非线性激活有关。
Small conductance (SK) calcium-activated potassium channels are found in many tissues throughout the body and open in response to elevations in intracellular calcium. In hippocampal neurons, SK channels are spatially co-localized with L-Type calcium channels. Due to the restriction of calcium transients into microdomains, only a limited number of L-Type Ca2+ channels can activate SK and, thus, stochastic gating becomes relevant. Using a stochastic model with calcium microdomains, we predict that intracellular Ca2+ fluctuations resulting from Ca2+ channel gating can increase SK2 subthreshold activity by 1–2 orders of magnitude. This effectively reduces the value of the Hill coefficient. To explain the underlying mechanism, we show how short, high-amplitude calcium pulses associated with stochastic gating of calcium channels are much more effective at activating SK2 channels than the steady calcium signal produced by a deterministic simulation. This stochastic amplification results from two factors: first, a supralinear rise in the SK2 channel’s steady-state activation curve at low calcium levels and, second, a momentary reduction in the channel’s time constant during the calcium pulse, causing the channel to approach its steady-state activation value much faster than it decays. Stochastic amplification can potentially explain subthreshold SK2 activation in unified models of both sub- and suprathreshold regimes. Furthermore, we expect it to be a general phenomenon relevant to many proteins that are activated nonlinearly by stochastic ligand release.
影响因子：
2.5
作者：
MIGLIORE, M;COOK, EP;JOHNSTON, D
通讯作者：
JOHNSTON, D
影响因子：
4
作者：
Shuai, JW;Parker, I
通讯作者：
Parker, I
影响因子：
7.2
作者：
Catterall, William A.
通讯作者：
Catterall, William A.