GABA modulates neurotransmission in sinus node via stimulation of GABAA receptor.
The neuromodulator role of gamma-aminobutyric acid (GABA) in the sinus node of the guinea pig heart was examined. GABA inhibited the electrical transmural stimulation (ETS)-evoked release of [3H]norepinephrine (NE) from the sinus node. Muscimol mimicked and bicuculline antagonized the inhibitory effect of GABA. However, the ETS-evoked release of [3H]NE was not inhibited by muscimol in the presence of atropine. The ETS-evoked release of [3H]acetylcholine (ACh) from the sinus node was enhanced by muscimol, and this effect was antagonized by bicuculline. As the ETS-evoked release of [3H]ACh was reduced by bicuculline alone, the endogenous GABA released by ETS is probably involved in the release of ACh. We propose that GABA, as a neuromodulator, inhibits activity of the adrenergic neuron due to stimulation of the cholinergic neuron via the GABAA receptor present in the sinus node.
Matsuyama
S
S
Department of Pharmacology, Kobe University School of Medicine, Japan.
Saito
N
N
Shuntoh
H
H
Taniyama
K
K
Tanaka
C
C
D000109:Acetylcholine / Q000378:metabolism; D000320:Adrenergic Fibers / Q000378:metabolism; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011963:Receptors, GABA-A / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D012849:Sinoatrial Node / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011963:Receptors, GABA-A; D014316:Tritium; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine; D009638:Norepinephrine; D001640:Bicuculline