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• W2058475057 abstract "Previous studies have shown that lidocaine and other local anesthetic drugs (LAs) cause use-dependent block of sodium current (I (Na)), 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 I (Na) 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." @default.
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• W2058475057 date "2010-10-28" @default.
• W2058475057 modified "2023-09-26" @default.
• W2058475057 title "Lidocaine partially depolarizes the S4 segment in domain IV of the sodium channel" @default.
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• W2058475057 doi "https://doi.org/10.1007/s00424-010-0894-1" @default.
• W2058475057 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3076088" @default.
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