Tsentsevitsky Andrei N, Khaziev Eduard F, Kovyazina Irina V, Petrov Alexey M
Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC "Kazan Scientific Center of RAS", P.o. Box 30, 420111, Kazan, Russia.
Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC "Kazan Scientific Center of RAS", P.o. Box 30, 420111, Kazan, Russia; Kazan State Medical University, Butlerov St., 49, 420008, Kazan, Russia.
Neuropharmacology. 2022 May 15;209:109021. doi: 10.1016/j.neuropharm.2022.109021. Epub 2022 Mar 1.
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 Ca transient and membrane permeability for K. The action of GIRK channel inhibition on evoked neurotransmission was prevented by selective antagonist of voltage-gated Ca channels of L-type. Furthermore, the effects of muscarinic acetylcholine receptor activation on neurotransmitter release, Ca 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 Ca channels. In addition, GIRK channels are key players in a feedback control of neurotransmitter release by muscarinic acetylcholine receptors.
G蛋白门控内向整流钾通道（GIRK通道）是神经元兴奋性的主要调节因子之一。中枢神经系统中GIRK通道的激活通常会导致突触后抑制。然而，GIRK通道在突触前过程中的功能，尤其是运动神经末梢的神经递质释放，尚未得到全面了解。在此，我们采用电生理和荧光方法，研究了GIRK通道在青蛙运动神经末梢神经递质释放中的作用。我们发现，用纳摩尔浓度的特律平-Q抑制GIRK通道可使胞吐事件与动作电位同步，但会抑制自发和诱发的神经递质释放，以及钙瞬变和钾离子的膜通透性。L型电压门控钙通道的选择性拮抗剂可阻止GIRK通道抑制对诱发神经传递的作用。此外，毒蕈碱型乙酰胆碱受体激活对神经递质释放、钙瞬变和钾通道活性的影响会因GIRK通道的抑制而受到显著调节。因此，在运动神经末梢，GIRK通道可调节神经递质释放的时间，并作为突触小泡胞吐作用的正向调节因子，部分通过L型钙通道发挥作用。此外，GIRK通道是毒蕈碱型乙酰胆碱受体对神经递质释放进行反馈控制的关键参与者。
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