Lidocaine partially depolarizes the S4 segment in domain IV of the sodium channel.
Lidocaine partially depolarizes the S4 segment in domain IV of the sodium channel.
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DOI：
10.1007/s00424-010-0894-1
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发表时间：
2011-01
影响因子：
4.5
通讯作者：
Hanck, Dorothy A.
中科院分区：
文献类型：
--
作者：
Sheets, Michael F.;Chen, Tiehua;Hanck, Dorothy A.
以往的研究表明，利多卡因和其他局部麻醉药(LAS)可引起使用依赖的钠电流(INA)阻断，即通过内孔药物结合与结构域III和IV中的S4之间的变构耦合，随着膜去极化而增加的阻断。MTSET保护实验证实LAS将DIIIS4稳定在向外的去极化位置。DIVS4的类似测试尚未见报道，尽管与非药物结合的钠(Na)通道相比，LAS可将DIV对总门控电荷的贡献减少约三分之一，并改变其运动，使其在−100 mV附近的负电位下贡献更多的门控电荷。为了研究利多卡因是否通过使DIVS4在静止时采取去极化位置或在去极化时限制其向外运动来降低DIVS4的门控电荷，我们在存在和不存在10 mM利多卡因的情况下对突变的Na通道R1628C(R3C-DIV)的INa进行了MTSET保护实验。结果表明，利多卡因使DIVS4呈现更强的去极化状态，这有利于DIVS4在去极化时的运动，导致在−10 0 mV附近产生过量的门控电荷。
Previous studies have shown that lidocaine and other local anesthetic drugs (LAs) cause use-dependent block of sodium current (INa), i.e., block that increases with membrane depolarization by allosteric coupling between drug binding in the inner pore and the S4s in domains III and IV. MTSET protection experiments have established that LAs stabilize DIIIS4 in an outward, depolarized position. Similar tests have not been reported for the DIVS4, although LAs have been shown to reduce DIV's contribution to total gating charge by about one third and to alter its movement such that it contributes more gating charge at negative potentials around −100 mV compared to non-drug-bound sodium (Na) channels. To investigate whether lidocaine reduces the gating charge of DIVS4 by causing it to adopt either a depolarized position at rest or by restricting its outward movement upon depolarization, we performed MTSET protection experiments on INa of the mutant Na channel, R1628C (R3C-DIV), in the presence and absence of 10 mM lidocaine. The results indicate that lidocaine causes the DIVS4 to assume a more depolarized position, which facilitates its movement upon depolarization leading to the excess gating charge at potentials near −100 mV.
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DOI：
10.1085/jgp.20028651
发表时间：
2003-02
期刊：
The Journal of general physiology
影响因子：
--
作者：
Sheets MF;Hanck DA
通讯作者：
Hanck DA
影响因子：
3.6
作者：
Nau, C;Wang, SY;Wang, GK
通讯作者：
Wang, GK
影响因子：
56.9
作者：
Long, SB;Campbell, EB;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
5.5
作者：
BEKKERS, JM;GREEFF, NG;NEUMCKE, B
通讯作者：
NEUMCKE, B
影响因子：
3.8
作者：
KHODOROV, BI
通讯作者：
KHODOROV, BI