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.
Department of Pharmacology, Kobe University School of Medicine, Japan.
S
S
Matsuyama
N
N
Saito
H
H
Shuntoh
K
K
Taniyama
C
C
Tanaka
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