Sodium channels as molecular targets for antiepileptic drugs

被引:183
作者
Ragsdale, DS
Avoli, M
机构
[1] McGill Univ, Montreal Neurol Inst, Cell Biol Excitable Tissues Grp, Montreal, PQ H3A 2B4, Canada
[2] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada
[3] McGill Univ, Dept Physiol, Montreal, PQ H3A 2B4, Canada
关键词
sodium channel; antiepileptic drug; phenytoin; carbamazepine; valproate; lamotrigine; topiramate;
D O I
10.1016/S0165-0173(97)00054-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Voltage-gated sodium channels mediate regenerative inward currents that are responsible for the initial depolarization of action potentials in brain neurons. Many of the most widely used antiepileptic drugs, as well as a number of promising new compounds suppress the abnormal neuronal excitability associated with seizures by means of complex voltage-and frequency-dependent inhibition of ionic currents through sodium channels. Over the past decade, advances in molecular biology have led to important new insights into the molecular structure of the sodium channel and have shed light on the relationship between channel structure and channel function. In this review, we examine how our current knowledge of sodium channel structure-function relationships contributes to our understanding of the action of anticonvulsant sodium channel blockers. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:16 / 28
页数:13
相关论文
共 114 条
[1]   Contribution of the S4 segment to gating charge in the Shaker K+ channel [J].
Aggarwal, SK ;
MacKinnon, R .
NEURON, 1996, 16 (06) :1169-1177
[2]  
[Anonymous], EPILEPSIA S2
[3]   CHARGE MOVEMENT ASSOCIATED WITH OPENING AND CLOSING OF ACTIVATION GATES OF NA CHANNELS [J].
ARMSTRONG, CM ;
BEZANILLA, F .
JOURNAL OF GENERAL PHYSIOLOGY, 1974, 63 (05) :533-552
[4]   DESTRUCTION OF SODIUM CONDUCTANCE INACTIVATION IN SQUID AXONS PERFUSED WITH PRONASE [J].
ARMSTRONG, CM ;
BEZANILLA, F ;
ROJAS, E .
JOURNAL OF GENERAL PHYSIOLOGY, 1973, 62 (04) :375-391
[5]   CURRENTS RELATED TO MOVEMENT OF GATING PARTICLES OF SODIUM CHANNELS [J].
ARMSTRONG, CM ;
BEZANILLA, F .
NATURE, 1973, 242 (5398) :459-461
[6]   A RAT-BRAIN NA+ CHANNEL ALPHA-SUBUNIT WITH NOVEL GATING PROPERTIES [J].
AULD, VJ ;
GOLDIN, AL ;
KRAFTE, DS ;
MARSHALL, J ;
DUNN, JM ;
CATTERALL, WA ;
LESTER, HA ;
DAVIDSON, N ;
DUNN, RJ .
NEURON, 1988, 1 (06) :449-461
[7]  
BAXTER MG, 1973, BRIT J PHARMACOL, V48, pP350
[8]   DIFFERENTIAL REGULATION OF 3 SODIUM-CHANNEL MESSENGER-RNAS IN THE RAT CENTRAL NERVOUS-SYSTEM DURING DEVELOPMENT [J].
BECKH, S ;
NODA, M ;
LUBBERT, H ;
NUMA, S .
EMBO JOURNAL, 1989, 8 (12) :3611-3616
[9]   ON THE MOLECULAR NATURE OF THE LIDOCAINE RECEPTOR OF CARDIAC NA+ CHANNELS - MODIFICATION OF BLOCK BY ALTERATIONS IN THE ALPHA-SUBUNIT III-IV INTERDOMAIN [J].
BENNETT, PB ;
VALENZUELA, C ;
CHEN, LQ ;
KALLEN, RG .
CIRCULATION RESEARCH, 1995, 77 (03) :584-592
[10]  
Biton V, 1996, NEUROLOGY, V46, P2024