Blockade of GABA uptake potentiates GABA-induced depolarizations in adult mouse cortical slices.
The electrophysiological effects of GABA and the GABA uptake inhibitor, NO-711, were investigated on cortical slices prepared from adult audiogenic seizure-prone DBA/2 mice. GABA, perfused for 1 min, elicited depolarizing responses which had a mean duration of 80-100 s and were concentration-dependent (0.1-32 mM). NO-711 (25 microM), perfused for 15 min, produced depolarizations with a mean duration of 50-60 s and these persisted for 4-5 h. The responses to both compounds were blocked by the GABA(A) receptor antagonist, bicuculline. Pre-treatment of the slices with NO-711 potentiated the responses to GABA and moved the concentration-response curve to the left. The EC50 to GABA following pre-treatment with NO-711 was 111+/-24 microM from a control value of 1.17+/-0.19 mM. These results demonstrate that in cortical slices GABA has a depolarizing action rather than the conventional one of hyperpolarization and that this response is potentiated by inhibition of GABA reuptake.
Davies
J A
JA
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff, UK. daviesja8@cf.ac.uk
Shakesby
A
A
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology*; D050485:GABA Plasma Membrane Transport Proteins; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D026901:Membrane Transport Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology*; D027361:Organic Anion Transporters; D010091:Oximes / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology*
D002352:Carrier Proteins; D018756:GABA Antagonists; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; D010091:Oximes; C078793:NNC 711; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline