Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels

被引:74
作者
Baron, Anne [1 ,2 ,3 ]
Diochot, Sylvie [1 ,2 ,3 ]
Salinas, Miguel [1 ,2 ,3 ]
Deval, Emmanuel [1 ,2 ,3 ]
Noel, Jacques [1 ,2 ,3 ]
Lingueglia, Eric [1 ,2 ,3 ]
机构
[1] CNRS, Inst Pharmacol Mol & Cellulaire, UMR 7275, F-06560 Valbonne, France
[2] Univ Nice Sophia Antipolis, F-06560 Valbonne, France
[3] LabEx Ion Channel Sci & Therapeut, F-06560 Valbonne, France
关键词
ASIC; Sodium channels; Toxins; Nervous system; Pathophysiology; Pain; EXERCISE PRESSOR REFLEX; ANEMONE ANTHOPLEURA-ELEGANTISSIMA; OPERATED CA2+ ENTRY; DORSAL-HORN NEURONS; SEA-ANEMONE; SENSORY NEURONS; SPINAL-CORD; EXTRACELLULAR ACIDOSIS; INFLAMMATORY PAIN; RETINAL FUNCTION;
D O I
10.1016/j.toxicon.2013.04.008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Acid-sensing ion channels (ASICs) are voltage-independent proton-gated cation channels that are largely expressed in the nervous system as well as in some non-neuronal tissues. In rodents, six different isoforms (ASIC1 a, lb, 2a, 2b, 3 and 4) can associate into homo- or hetero-trimers to form a functional channel. Specific polypeptide toxins targeting ASIC channels have been isolated from the venoms of spider (PcTx1), sea anemone (APETx2) and snakes (MitTx and mambalgins). They exhibit different and sometimes partially overlapping pharmacological profiles and are usually blockers of ASIC channels, except for MitTx, which is a potent activator. This review focuses on the use of these toxins to explore the structure function relationships, the physiological and the pathophysiological roles of ASIC channels, illustrating at the same time the therapeutic potential of some of these natural compounds. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:187 / 204
页数:18
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