Mg2+ enhances voltage sensor/gate coupling in BK channels.
Mg2+ enhances voltage sensor/gate coupling in BK channels.
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MG2+增强了BK通道中的电压传感器/门耦合。
DOI：
10.1085/jgp.200709877
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发表时间：
2008-01
影响因子：
3.8
通讯作者：
Ma, Zhongming
中科院分区：
文献类型：
--
作者：
Horrigan, Frank T.;Ma, Zhongming
BK (Slo1) 钾通道由毫摩尔细胞内 Mg2+ 以及微摩尔 Ca2+ 和膜去极化激活。 Mg2+ 和 Ca2+ 在不同的结合位点以近似相加的方式起作用，以改变电导电压 (GK-V) 关系，表明这些配体可能通过功能相似但独立的机制发挥作用。然而，我们发现 Mg2+ 的作用机制高度依赖于电压传感器的激活，因此与 Ca2+ 的作用机制有根本的不同。 Ca2+ 独立于电压传感器激活而起作用的证据包括在电压传感器处于静止状态的极端负电压下增加开路概率 (PO) 的能力；在-120 mV 下，2 μM Ca2+ 可使 PO 增加 15 倍以上。然而，当电压传感器处于静止状态时，10 mM Mg2+ 对 GK-V 关系的影响与 2 μM Ca2+ 类似，但对 PO 没有可检测到的影响。当通道关闭时，Mg2+ 仅轻微改变门控电流，这表明 Mg2+ 不仅仅起到促进电压传感器激活的作用。事实上，在电压传感器被组成性激活的突变体（R210C）中，Mg2+以电压无关的方式促进通道开放。因此，10 mM Mg2+ 仅在电压传感器激活时增加 PO，从而有效加强电压传感器激活与通道开放的变构耦合。将 Mg2+ 从 10 mM 增加到 100 mM，以占据非常低亲和力的结合位点，对门控具有更类似于 Ca2+ 的额外影响。 Mg2+ 对稳态激活和 IK 动力学的影响根据变构门控方案以及 Mg2+ 和电压传感器之间可能构成该机制的状态依赖性相互作用进行了讨论。
BK (Slo1) potassium channels are activated by millimolar intracellular Mg2+ as well as micromolar Ca2+ and membrane depolarization. Mg2+ and Ca2+ act in an approximately additive manner at different binding sites to shift the conductance–voltage (GK-V) relation, suggesting that these ligands might work through functionally similar but independent mechanisms. However, we find that the mechanism of Mg2+ action is highly dependent on voltage sensor activation and therefore differs fundamentally from that of Ca2+. Evidence that Ca2+ acts independently of voltage sensor activation includes an ability to increase open probability (PO) at extreme negative voltages where voltage sensors are in the resting state; 2 μM Ca2+ increases PO more than 15-fold at −120 mV. However 10 mM Mg2+, which has an effect on the GK-V relation similar to 2 μM Ca2+, has no detectable effect on PO when voltage sensors are in the resting state. Gating currents are only slightly altered by Mg2+ when channels are closed, indicating that Mg2+ does not act merely to promote voltage sensor activation. Indeed, channel opening is facilitated in a voltage-independent manner by Mg2+ in a mutant (R210C) whose voltage sensors are constitutively activated. Thus, 10 mM Mg2+ increases PO only when voltage sensors are activated, effectively strengthening the allosteric coupling of voltage sensor activation to channel opening. Increasing Mg2+ from 10 to 100 mM, to occupy very low affinity binding sites, has additional effects on gating that more closely resemble those of Ca2+. The effects of Mg2+ on steady-state activation and IK kinetics are discussed in terms of an allosteric gating scheme and the state-dependent interactions between Mg2+ and voltage sensor that may underlie this mechanism.
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影响因子：
2.9
作者：
Cui, JM;Aldrich, RW
通讯作者：
Aldrich, RW
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.109.5.647
发表时间：
1997-05
期刊：
The Journal of general physiology
影响因子：
--
作者：
Cui J;Cox DH;Aldrich RW
通讯作者：
Aldrich RW
影响因子：
3.4
作者：
Avdonin, V;Tang, XD;Hoshi, T
通讯作者：
Hoshi, T
影响因子：
16.2
作者：
Jiang, YX;Pico, A;MacKinnon, R
通讯作者：
MacKinnon, R