GIRK channel as a versatile regulator of neurotransmitter release via L-type Ca2+ channel-dependent mechanism in the neuromuscular junction.

G protein-gated inwardly rectifying potassium (GIRK) channels are one of the main regulators of neuronal excitability. Activation of GIRK channels in the CNS usually leads to postsynaptic inhibition. However, the function of GIRK channels in the presynaptic processes, notably neurotransmitter release form motor nerve terminals, is yet to be comprehensively understood. Here, using electrophysiological and fluorescent approaches, the role of GIRK channels in neurotransmitter release from frog motor nerve terminals was studied. We found that the inhibition of GIRK channels with nanomolar tertiapin-Q synchronized exocytosis events with action potential but suppressed spontaneous and evoked neurotransmitter release, as well as Ca2+ transient and membrane permeability for K+. The action of GIRK channel inhibition on evoked neurotransmission was prevented by selective antagonist of voltage-gated Ca2+ channels of L-type. Furthermore, the effects of muscarinic acetylcholine receptor activation on neurotransmitter release, Ca2+ transient and K+ channel activity were markedly modulated by inhibition of GIRK channels. Thus, at the motor nerve terminals GIRK channels can regulate timing of neurotransmitter release and be a positive modulator of synaptic vesicle exocytosis acting partially via L-type Ca2+ channels. In addition, GIRK channels are key players in a feedback control of neurotransmitter release by muscarinic acetylcholine receptors.