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Effects of gamma-aminobutyric acid (GABA) and some selective GABAergic ligands on the quantal acetylcholine (ACh) release in the frog neuromuscular contacts were investigated using combination of microelectrode technique with fluorescent and immunohistochemical assays. Significant attenuation of ACh release was observed in the presence of GABA as well as selective GABAA and GABAB receptor agonists. Neither GABAA nor GABAB antagonists abolished to full extent this effect of GABA. Fluorescent assay allowed to detect the GABA-induced opening of K+ channels, which was inhibited by XE-991, a selective antagonist of Kv7 type. Electrophysiological recordings of endplate potentials in the presence of XE-991 confirmed the contribution of Kv7 type potassium channels to the effects of GABA on ACh release that was not associated with GABAA and GABAB receptors activation. Note that XE-991 effectively precluded the action of retigabine, neuronal Kv7 channel opener, on ACh release. Immunohistochemical assay revealed that frog mature skeletal muscle fibers contain a significant amount of GABA, and substantial amount of GABA can be released in the extracellular space at the muscle contractions induced by prolonged high-frequency nerve stimulation. Besides, some binding sites for exogenous GABA were detected on the plasma membranes. It is concluded that GABA, in addition to affecting GABAA and GABAB receptors, can directly activate Kv7 channels, thereby negatively modulating the evoked ACh release. Endogenous GABA may serve as a retrograde regulator of neurotransmitter exocytosis.Highlights: GABA attenuates ACh release in frog NMJ acting on GABAA, GABAB receptors, and Kv7 channels. GABA directly, in a voltage-independent manner, activates Kv7 channels in frog NMJ. GABA is present in skeletal muscle fibers and can be released during the muscle activity. [ABSTRACT FROM AUTHOR]

Studies the dependence of miniature endplate current (MEPC) amplitude and temporal parameters on the values of the rate constants of acetylcholine binding to receptors when cholinesterase was either active or inactive. Small probability of nicotinic acetylcholine receptor forward isomerization after acetylcholine binding and faster MEPC peak formation; Analysis of pertinent topics and relevant issues; Implications on neurochemistry research.