GABA(A) and GABA(C) receptors have contrasting effects on excitability in superior colliculus.
We have recently found that GABA(C) receptor subunit transcripts are expressed in the superficial layers of rat superior colliculus (SC). In the present study we used immunocytochemistry to demonstrate the presence of GABA(C) receptors in rat SC at protein level. We also investigated in acute rat brain slices the effect of GABA(A) and GABA(C) receptor agonists and antagonists on stimulus-evoked extracellular field potentials in SC. Electrical stimulation of the SC optic layer induced a biphasic, early and late, potential in the adjacent superficial layer. The late component was completely inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione or CoCl(2), indicating that it was generated by postsynaptic activation. Muscimol, a potent GABA(A) and GABA(C) receptor agonist, strongly attenuated this postsynaptic potential at concentrations >10 microM. In contrast, the GABA(C) receptor agonist cis-aminocrotonic acid, as well as muscimol at lower concentrations (0.1-1 microM) increased the postsynaptic potential. This increase was blocked by (1,2,5, 6-tetrahydropyridine-4-yl)methylphosphinic acid, a novel competitive antagonist of GABA(C) receptors. Our findings demonstrate the presence of functional GABA(C) receptors in SC and suggest a disinhibitory role of these receptors in SC neuronal circuitry.
Pasternack
M
M
Institute of Biotechnology, University of Helsinki, FIN-00014 Helsinki, Finland.
Boller
M
M
Pau
B
B
Schmidt
M
M
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D003035:Cobalt / Q000494:pharmacology; D004558:Electric Stimulation; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D013477:Superior Colliculi / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; C087200:GABA-C receptor; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D009118:Muscimol; D003035:Cobalt; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D008012:Lidocaine; C018021:cobaltous chloride