Bidirectional regulations for glutamate and GABA release in the hippocampus by alpha7 and non-alpha7 ACh receptors.
In the assay of glutamate and gamma-aminobutyric acid (GABA) with a high-performance liquid chromatography, spontaneous release of glutamate and GABA from rat hippocampal slices was significantly enhanced by mecamylamine, an inhibitor of non-alpha7 ACh receptors, or alpha-bungarotoxin, an inhibitor of alpha7 ACh receptors in the absence of tetrodotoxin (TTX), but not in the presence of TTX. Nicotine significantly enhanced glutamate and GABA release in the absence of TTX, that is abolished by mecamylamine or alpha-bungarotoxin, while it had no effect on the release in the presence of TTX. In the recording of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated excitatory postsynaptic currents (AMPA-EPSCs) and GABA(A) receptor-mediated inhibitory postsynaptic currents (GABA(A)-IPSCs) from CA1 pyramidal neurons of rat hippocampal slices, nicotine did not affect the rate and amplitude of AMPA-EPSCs and AMPA-miniature EPSCs. In contrast, nicotine significantly increased the rate of GABA(A)-IPSCs, without affecting the amplitude, but such effect was not obtained with GABA(A)-miniature IPSCs. The collective results suggest that alpha7 and non-alpha7 ACh receptors expressed in the hippocampus, activated under the basal conditions, inhibit release of glutamate and GABA controlled through multi-synaptic relays, but that otherwise, those receptors, highly activated by nicotine, stimulate both the release, with a part of GABA released from interneurons transmitting to CA1 pyramidal neurons. Furthermore, the results also suggest that alpha7 and non-alpha7 ACh receptors do not have potency sufficiently to modulate glutamate and GABA release controlled by single synapses.
Kanno
Takeshi
T
Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
Yaguchi
Takahiro
T
Yamamoto
Satoshi
S
Nagata
Tetsu
T
Yamamoto
Hideyuki
H
Fujikawa
Hirokazu
H
Nishizaki
Tomoyuki
T
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C579165:Chrna7 protein, rat; D018377:Neurotransmitter Agents; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid