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Effects of pyrethroid molecules on rat nerves in vitro: potential to reverse temperature-sensitive conduction block of demyelinated peripheral axons.

Abstract：

:1. Prolongation of action potentials by cooling or pharmacological treatment can restore conduction in demyelinated axons. We have assessed the ability of pyrethroids (in vitro) to modify action potential kinetics and to reverse conduction block in lesioned peripheral nerve. 2. Fast Na+ currents were isolated in mammalian neuroblastoma (NIE115). Pyrethroids (4 microM) concurrently slowed inactivation and produced a spectrum of pronounced tail currents: s-bioallethrin (duration 12.2+/-7 ms), permethrin (24.2+/-3 ms) and deltamethrin (2230+/-100 ms). 3. Deltamethrin (5 microM) effected a slowly developing depression of compound action potential (CAP) amplitude in peroneal nerve trunks (P<0.05). Permethrin produced no net effect on CAP amplitude, area or repolarization time. 4. s-Bioallethrin (5 microM) enhanced CAP area, time for 90% repolarization and induced regenerative activity in a subpopulation of axons. 5. Tibial nerve trunks were demyelinated by lysolecithin (2 micro1) injection: 6-14 days later, slowly-conducting axons in the CAP (and peri-axonal microelectrode recordings) were selectively blocked by warming to 37 degrees C. 6. At 37 degrees C, s-bioallethrin (45 min, 5 microM) produced much greater after-potentials in lesioned nerves than in uninjected controls: area (P< 0.05) and relative amplitude ratios (P< 0.0001) were significantly altered. 7. In 3 of 4 cells (single-unit recording), s-bioallethrin restored conduction through axons exhibiting temperature-dependent block by raising blocking temperature (by 1.5 to > 3 degrees C) and reducing refractory period. 8. s-Bioallethrin induced temperature-dependent regenerative activity only in a sub-population of axons even after prolonged superfusion (> 1 h). 9. It was concluded that pyrethroids differentially alter Na+ current kinetics and action potential kinetics. The effects of s-bioallethrin are consistent with reversal of conduction block by demyelinated axons but regenerative/ectopic firing even in normal cells is likely to underpin its acknowledged neurotoxic actions and severely limit the clinical potential of this and related molecules.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Lees G

doi

10.1038/sj.bjp.0701644

subject

Has Abstract

pub_date

1998-02-01 00:00:00

pages

487-96

issue

eissn

0007-1188

issn

1476-5381

journal_volume

123

pub_type

杂志文章

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Effects of pyrethroid molecules on rat nerves in vitro: potential to reverse temperature-sensitive conduction block of demyelinated peripheral axons.