Age-Dependent Regulation of Acetylcholine Release at the Neuromuscular Junction Mediated by GABA.

γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system. However, GABA receptors, notably at the neuromuscular junction (NMJ), have also been identified in the peripheral nervous system. Here, we studied GABAB receptor (GABAB-R)-mediated regulation of acetylcholine (ACh) release in mouse NMJs during early postnatal development. The results revealed that, depending on the age of the mice, the activation of GABAB-R had the opposite effect on ACh release. At the NMJ in mice on the second postnatal (P2) day, the GABAB-R blocker CGP 55845 (5 μM) significantly increased the level of ACh release, whereas the GABAB-R agonist baclofen (10 μM) decreased ACh release. In P14-aged mice, CGP 55845 decreased ACh release, while the application of baclofen significantly increased the release. At the NMJ of P14 mice, the mechanism of the ACh release-potentiating effect of GABAB-R activation involves N-type calcium ion channels and small-conductance calcium ion-activated potassium ion channels.