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Potent and voltage‐dependent block by philanthotoxin‐343 of neuronal nicotinic receptor/channels in PC12 cells
Author(s) -
Liu Min,
Nakazawa Ken,
Inou Kazuhide,
Ohno Yasuo
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701373
Subject(s) - depolarization , biophysics , nicotinic agonist , patch clamp , voltage clamp , acetylcholine receptor , neurotoxin , nicotinic acetylcholine receptor , ion channel , electrophysiology , acetylcholine , biology , neuroscience , membrane potential , chemistry , receptor , biochemistry , endocrinology
1 Block by philanthotoxin‐343 (PhTX‐343), a neurotoxin from wasps, of ionic currents mediated through neuronal nicotinic acetylcholine (ACh) receptor/channels was characterized in rat phaeochromocytoma PC12 cells, by use of whole cell voltage‐clamp techniques. 2 In the cells held at −60 mV, PhTX‐343 at 0.1 and 1 μ M inhibited an inward current activated by 100 μ M ACh. The current inhibition was relieved by depolarizing steps, and augmented at negative potentials, suggesting that PhTX‐343 blocks the channel in a voltage‐dependent manner. Joro spider toxin‐3 (JSTX‐3) also exerted voltage‐dependent inhibition of ACh‐activated currents in a similar concentration range, but argiotoxin636 did not affect the currents. 3 Analysis of the current decay during hyperpolarizing steps indicated that the current inhibition by 100 n M PhTX‐343 develops in an order of several hundreds of milliseconds. On the other hand, the recovery from the current inhibition during depolarizing steps developed in an order of about 100 ms. 4 The results suggest that PhTX‐343 blocks neuronal nicotinic receptor channels in PC12 cells at concentrations lower than those required for channel block in non‐mammalian cells, and the block exhibits clear voltage‐dependence. Estimated from the voltage‐dependence, the binding site of PhTX‐343 may be located near the outer mouth of the channel.British Journal of Pharmacology (1997) 122 , 379–385; doi: 10.1038/sj.bjp.0701373