...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Computational Neuroscience >Stochastic amplification of calcium-activated potassium currents in Ca~(2+) microdomains
【24h】

Stochastic amplification of calcium-activated potassium currents in Ca~(2+) microdomains

机译：Ca〜（2+）微区中钙激活钾电流的随机放大

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Small conductance (SK) calcium-activated potassium channels are found in many tissues throughout the body and open in response to elevations in in-tracellular 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 Ca~(2+) channels can activate SK and, thus, stochastic gating becomes relevant. Using a stochastic model with calcium microdomains, we predict that intracellular Ca~(2+) fluctuations resulting from Ca~(2+) 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.
机译：在人体的许多组织中都发现了小电导（SK）钙激活的钾通道，并随着细胞内钙的升高而开放。在海马神经元中，SK通道与L型钙通道在空间上共定位。由于钙瞬态进入微区的限制，只有有限数量的L型Ca〜（2+）通道可以激活SK，因此，随机门控变得很重要。使用具有钙微结构域的随机模型，我们预测由Ca〜（2+）通道门控引起的细胞内Ca〜（2+）波动可将SK2亚阈值活性提高1-2个数量级。这有效地减小了希尔系数的值。为了解释潜在的机制，我们显示了与随机触发的钙通道相关的短高振幅钙脉冲在激活SK2通道方面比确定性模拟产生的稳定钙信号有效得多。这种随机放大是由两个因素造成的：首先，在低钙水平下，SK2通道的稳态激活曲线超线性上升；其次，在钙脉冲期间，通道时间常数的瞬时减少，导致通道接近其稳定状态。状态激活值比其衰减快得多。随机扩增可以潜在地解释亚阈值和超阈值机制的统一模型中的亚阈值SK2激活。此外，我们希望这是与随机配体释放非线性激活的许多蛋白质有关的普遍现象。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号