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.