Actions of anaesthetics and avermectin on GABAA chloride channels in mammalian dorsal root ganglion neurones.
1. The gamma-aminobutyric acid (GABA)-mimetic actions of some anaesthetics and the antehelminthic avermectin B1a 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 microM-3 mM), chloralose (600 microM-1 mM), etomidate (10-100 microM), alphaxalone (10-60 microM) and avermectin (10-60 microM) 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.
Robertson
B
B
Department of Physiology, John Curtin School of Medical Research, Australian National University, Canberra.
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D009126:Muscle Relaxation / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000777:Anesthetics; D002712:Chlorides; D007473:Ion Channels; D005680:gamma-Aminobutyric Acid; D007559:Ivermectin; C019264:avermectin; D010424:Pentobarbital