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Actions of anaesthetics and avermectin on GABA A chloride channels in mammalian dorsal root ganglion neurones
Author(s) -
Robertson Brian
Publication year - 1989
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 - 10.1111/j.1476-5381.1989.tb16878.x
Subject(s) - bicuculline , chemistry , dorsal root ganglion , chloride channel , biophysics , muscimol , picrotoxin , voltage clamp , electrophysiology , agonist , gaba receptor antagonist , gabaa receptor , pharmacology , anatomy , membrane potential , neuroscience , biochemistry , dorsum , receptor , biology
1 The γ‐aminobutyric acid (GABA)‐mimetic actions of some anaesthetics and the antehelminthic avermectin B 1a were examined on freshly isolated mammalian dorsal root ganglion (DRG) neurones by use of suction electrodes and a single electrode voltage clamp. 2 Pentobarbitone (60 μ m ‐3 mM), chloralose (600 μ m ‐1 mM), etomidate (10–100 μ m ), alphaxalone (10–60 μ m ) and avermectin (10–60 μ m ) directly activated chloride channels in GABA‐sensitive DRG neurones. The agonist action was sensitive to block by bicuculline and picrotoxinin. 3 Steady‐state current‐voltage (I‐V) curves for the anaesthetics were either linear, or rectified in the opposite direction to steady‐state I‐V curves obtained with GABA. Current relaxations in response to voltage jumps were also of the opposite direction. An extra surge of current (‘bounce’) was commonly observed on washout of some of these agonists. 4 Pentobarbitone was ineffective as an agonist at alkali pH (10.4 and 9.4), but was approximately twice as effective at acid (5.4) than at normal (7.4) pH values. 5 These results suggest that some anaesthetics and avermectin are capable of ‘blocking’ GABA channels in addition to activating them.