title: Kinetics of GABAB autoreceptor-mediated suppression of GABA release in rat insular cortex.
abstract: Release of GABA is controlled by presynaptic GABA receptor type B (GABA(B)) autoreceptors at GABAergic terminals. However, there is no direct evidence that GABA(B) autoreceptors are activated by GABA release from their own terminals, and precise profiles of GABA(B) autoreceptor-mediated suppression of GABA release remain unknown. To explore these issues, we performed multiple whole-cell, patch-clamp recordings from layer V rat insular cortex. Both unitary inhibitory and excitatory postsynaptic currents (uIPSCs and uEPSCs, respectively) were recorded by applying a five-train depolarizing pulse injection at 20 Hz. In connections from both fast-spiking (FS) and non-FS interneurons to pyramidal cells, the GABA(B) receptor antagonist CGP 52432 had little effect on the initial uIPSC amplitude. However, uIPSCs, responding to later pulses, were effectively facilitated. This CGP 52432-induced facilitation was prominent in the fourth uIPSCs, which were evoked 150 ms after the first uIPSC. The facilitation of uIPSCs was accompanied by an increase in the paired-pulse ratio. In addition, analysis of the coefficient of variation suggests the involvement of presynaptic mechanisms in CGP 52432-induced uIPSC facilitation. Paired-pulse stimulation (interstimulus interval = 150 ms) of presynaptic FS cells revealed that the second uIPSC was also facilitated by CGP 52432, which had little effect on the amplitude and interevent interval of miniature IPSCs. In contrast, uEPSCs, responding to all five stimulations of a presynaptic pyramidal cell, were less affected by CGP 52432. These results suggest that a single presynaptic action potential is sufficient to activate GABA(B) autoreceptors and to suppress GABA release in the cerebral cortex.
authors.affiliation: Dept. of Pharmacology, Nihon Univ. School of Dentistry, Tokyo, Japan. kobayashi-ms@dent.nihon-u.ac.jp
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takei
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Hatanaka
authors.forename: Noriaki
authors.initials: N
authors.lastname: Koshikawa
mesh_terms: D000818:Animals; D017660:Autoreceptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D055647:Rats, Transgenic; D018080:Receptors, GABA-B / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D017660:Autoreceptors; D058788:GABA-B Receptor Antagonists; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid