alpha7 nicotinic acetylcholine receptors and modulation of gabaergic synaptic transmission in the hippocampus.
The present report provides new findings regarding modulation of gamma-aminobutyric acid (GABA) transmission by alpha7 nicotinic receptor activity in CA1 interneurons of rat hippocampal slices. Recordings were obtained from tight-seal cell-attached patches of the CA1 interneurons, and agonists were delivered to the neurons via a modified U-tube. Application for 6 s of the alpha7 nicotinic receptor-selective agonist choline (> or =1 mM) to all CA1 interneurons tested triggered action potentials that were detected as fast current transients. The activity triggered by choline terminated well before the end of the agonist pulse, was blocked by the alpha7 nicotinic receptor antagonist methyllycaconitine (50 nM) and was concentration dependent; the higher the concentration of choline the higher the frequency of events and the shorter the delay for detection of the first event. In 40% of the neurons tested, choline-triggered action potentials decreased in amplitude progressively until no more events could be detected despite the presence of the agonist. Primarily, this finding could be explained by Na(+)-channel inactivation associated with membrane depolarization induced by alpha7 nicotinic receptor activation. In 60% of the neurons, the amplitude of choline-induced action potentials was sustained at the intial level, but again the activity did not last as long as the agonist pulse, in this case apparently because of agonist-induced receptor desensitization. These results altogether demonstrate that agonists interacting with alpha7 nicotinic receptors, including the natural transmitter acetylcholine and its metabolite choline, influence GABAergic transmission, not only by activating these receptors, but also by controlling the rate of Na(+)-channel inactivation and/or by inducing receptor desensitization.
Alkondon
M
M
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Braga
M F
MF
Pereira
E F
EF
Maelicke
A
A
Albuquerque
E X
EX
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002794:Choline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology*; D009435:Synaptic Transmission; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
C579165:Chrna7 protein, rat; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005680:gamma-Aminobutyric Acid; D002794:Choline