Intrinsic voltage dependence and Ca2+ regulation of mslo large conductance Ca-activated K+ channels.
Intrinsic voltage dependence and Ca2+ regulation of mslo large conductance Ca-activated K+ channels.
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DOI：
10.1085/jgp.109.5.647
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发表时间：
1997-05
期刊：
影响因子：
--
通讯作者：
Aldrich RW
中科院分区：
文献类型：
--
作者：
Cui J;Cox DH;Aldrich RW
在非洲爪蟾卵母细胞切除斑块中研究了宏观mslo钙活化K+电流的动力学和稳态特性。作为对电压阶跃的响应，激活和失活的时间过程，除了激活的短暂延迟，可以用一个单一的指数函数在宽范围的电压和内部Ca2+浓度（[Ca]i）上近似。激活率随电压和[Ca]i的增加而增加，在高[Ca]i时接近饱和。失活率一般随[Ca]i和电压的增加而降低，在高[Ca]i时接近饱和。随着[Ca]i的增加，宏观电导随电压（G-V）和激活和失活时间常数的函数图沿电压轴向左移动。G-V关系可以用玻尔兹曼函数近似表示，当[Ca]i在0.84 ~ 1000 μM之间变化时，等效门控电荷在1.1 ~ 1.8 e之间。Hill分析表明，至少有三个Ca2+结合位点可以促进通道激活。三条线的证据表明，至少有一个电压依赖的单分子构象变化与钙离子结合分离的mslo门控相关。(a) mslo - G-V关系的位置不随[Ca]i呈对数变化。(b)在高[Ca]i时，宏观活化速率常数接近饱和，但仍与电压有关。(c)在强去极化的情况下，mslo电流几乎可以在不结合Ca2+的情况下被最大限度地激活。这些结果可以理解为通道必须经历一个中心电压依赖的速率限制构象变化，以便从关闭到打开，快速Ca2+结合到打开和关闭状态调节这个中心步骤。
The kinetic and steady-state properties of macroscopic mslo Ca-activated K+ currents were studied in excised patches from Xenopus oocytes. In response to voltage steps, the timecourse of both activation and deactivation, but for a brief delay in activation, could be approximated by a single exponential function over a wide range of voltages and internal Ca2+ concentrations ([Ca]i). Activation rates increased with voltage and with [Ca]i, and approached saturation at high [Ca]i. Deactivation rates generally decreased with [Ca]i and voltage, and approached saturation at high [Ca]i. Plots of the macroscopic conductance as a function of voltage (G-V) and the time constant of activation and deactivation shifted leftward along the voltage axis with increasing [Ca]i. G-V relations could be approximated by a Boltzmann function with an equivalent gating charge which ranged between 1.1 and 1.8 e as [Ca]i varied between 0.84 and 1,000 μM. Hill analysis indicates that at least three Ca2+ binding sites can contribute to channel activation. Three lines of evidence indicate that there is at least one voltage-dependent unimolecular conformational change associated with mslo gating that is separate from Ca2+ binding. (a) The position of the mslo G-V relation does not vary logarithmically with [Ca]i. (b) The macroscopic rate constant of activation approaches saturation at high [Ca]i but remains voltage dependent. (c) With strong depolarizations mslo currents can be nearly maximally activated without binding Ca2+. These results can be understood in terms of a channel which must undergo a central voltage-dependent rate limiting conformational change in order to move from closed to open, with rapid Ca2+ binding to both open and closed states modulating this central step.
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影响因子：
16.2
作者：
Aggarwal, SK;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
64.8
作者：
GETZOFF, ED;CABELLI, DE;HALLEWELL, RA
通讯作者：
HALLEWELL, RA
内部BA2+与平滑肌的克隆Ca（2+） - 依赖性K+（HSLO）通道的相互作用。
影响因子：
3.8
作者：
Diaz, F;Wallner, M;Stefani, E;Toro, L;Latorre, R
通讯作者：
Latorre, R
DOI：
10.1085/jgp.105.1.49
发表时间：
1995-01
期刊：
The Journal of general physiology
影响因子：
--
作者：
Art JJ;Wu YC;Fettiplace R
通讯作者：
Fettiplace R
影响因子：
3.4
作者：
HEGINBOTHAM, L;LU, Z;MACKINNON, R
通讯作者：
MACKINNON, R