Lidocaine induces a slow inactivated state in rat skeletal muscle sodium channels

被引:56
作者
Chen, ZH
Ong, BH
Kamouris, NG
Marbán, E
Tomaselli, GF
Balser, JR
机构
[1] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37212 USA
[2] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA
[3] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Sch Med, Inst Mol Cardiobiol, Baltimore, MD 21205 USA
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2000年 / 524卷 / 01期
关键词
D O I
10.1111/j.1469-7793.2000.t01-1-00037.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. Local anaesthetics such as lidocaine (lignocaine) interact with sodium channels in a manner that is exquisitely sensitive to the voltage-dependent conformational state of the ion channel. When depolarized in the presence of lidocaine, sodium channels assume a long-lived quiescent state. Although studies over the last decade have localized the lidocaine receptor to the inner aspect of the aqueous pore, the mechanistic basis of depolarization-induced 'use-dependent' lidocaine block remains uncertain. 2. Recent studies have shown that lowering the extracellular Na+ concentration ([Na+](o)) and mutations in the sodium channel outer P-loop modulate occupancy of a quiescent 'slow' inactivated state with intermediate kinetics (termed I-M) that involves structural rearrangements in the outer pore. 3. Site-directed mutagenesis and ion-replacement experiments were performed using voltage-clamped Xenopus oocytes and cultured (HEK-293) cells expressing wild-type and mutant rat skeletal muscle (mu l) sodium channels. 4. Our results show that lowering [Na+](o) potentiates use-dependent lidocaine block. The effect of [Na+](o) is maintained despite a III-IV linker mutation that partially disrupts fast inactivation (F1304Q). In contrast, the effect of lowering [Na+](o) on lidocaine block is reduced by a P-loop mutation (W402A) that limits occupancy of I-M. 5. Our findings are consistent with a simple allosteric model where lidocaine binding induces channels to occupy a native slow inactivated state that is inhibited by [Na+](o).
引用
收藏
页码:37 / 49
页数:13
相关论文
共 67 条
[1]   EFFECTS OF EXTERNAL POTASSIUM AND LONG DURATION VOLTAGE CONDITIONING ON AMPLITUDE OF SODIUM CURRENTS IN GIANT AXON OF SQUID, LOLIGO P5ALEI [J].
ADELMAN, WJ ;
PALTI, Y .
JOURNAL OF GENERAL PHYSIOLOGY, 1969, 54 (05) :589-&
[2]   GLOBAL PARAMETER OPTIMIZATION FOR CARDIAC POTASSIUM CHANNEL GATING MODELS [J].
BALSER, JR ;
RODEN, DM ;
BENNETT, PB .
BIOPHYSICAL JOURNAL, 1990, 57 (03) :433-444
[3]   Functional consequences of lidocaine binding to slow-inactivated sodium channels [J].
Balser, JR ;
Nuss, HB ;
Romashko, DN ;
Marban, E ;
Tomaselli, GF .
JOURNAL OF GENERAL PHYSIOLOGY, 1996, 107 (05) :643-658
[4]   External pore residue mediates slow inactivation in mu 1 rat skeletal muscle sodium channels [J].
Balser, JR ;
Nuss, HB ;
Chiamvimonvat, N ;
PerezGarcia, MT ;
Marban, E ;
Tomaselli, GF .
JOURNAL OF PHYSIOLOGY-LONDON, 1996, 494 (02) :431-442
[5]   Local anesthetics as effectors of allosteric gating - Lidocaine effects on inactivation-deficient rat skeletal muscle Na channels [J].
Balser, JR ;
Nuss, HB ;
Orias, DW ;
Johns, DC ;
Marban, E ;
Tomaselli, GF ;
Lawrence, JH .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 98 (12) :2874-2886
[6]   BLOCKADE OF CARDIAC SODIUM-CHANNELS - COMPETITION BETWEEN THE PERMEANT ION AND ANTIARRHYTHMIC DRUGS [J].
BARBER, MJ ;
WENDT, DJ ;
STARMER, CF ;
GRANT, AO .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (02) :368-381
[7]   Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel [J].
Baukrowitz, T ;
Yellen, G .
SCIENCE, 1996, 271 (5249) :653-656
[8]   LIDOCAINE BLOCK OF CARDIAC SODIUM-CHANNELS [J].
BEAN, BP ;
COHEN, CJ ;
TSIEN, RW .
JOURNAL OF GENERAL PHYSIOLOGY, 1983, 81 (05) :613-642
[9]  
Bénitah JP, 1999, J NEUROSCI, V19, P1577
[10]   Molecular motions within the pore of voltage-dependent sodium channels [J].
Benitah, JP ;
Ranjan, R ;
Yamagishi, T ;
Janecki, M ;
Tomaselli, GF ;
Marban, E .
BIOPHYSICAL JOURNAL, 1997, 73 (02) :603-613