Department of Pharmacy, School of Medicine, University of Naples Federico II, Naples, Italy.
Department of Neuroscience, University of Turin, Turin, Italy.
Cerebellum. 2020 Dec;19(6):751-761. doi: 10.1007/s12311-020-01158-y.
G-protein-coupled inwardly rectifying potassium (GIRK) channels contribute to the resting membrane potential of many neurons and play an important role in controlling neuronal excitability. Although previous studies have revealed a high expression of GIRK subunits in the cerebellum, their functional role has never been clearly described. Using patch-clamp recordings in mice cerebellar slices, we examined the properties of the GIRK currents in Purkinje cells (PCs) and investigated the effects of a selective agonist of GIRK1-containing channels, ML297 (ML), on PC firing and synaptic plasticity. We demonstrated that GIRK channel activation decreases the PC excitability by inhibiting both sodium and calcium spikes and, in addition, modulates the complex spike response evoked by climbing fiber stimulation. Our results indicate that GIRK channels have also a marked effect on synaptic plasticity of the parallel fiber-PC synapse, as the application of ML297 increased the expression of LTP while preventing LTD. We, therefore, propose that the recruitment of GIRK channels represents a crucial mechanism by which neuromodulators can control synaptic strength and membrane conductance for proper refinement of the neural network involved in memory storage and higher cognitive functions.
G 蛋白偶联内向整流钾 (GIRK) 通道有助于许多神经元的静息膜电位，并在控制神经元兴奋性方面发挥重要作用。尽管先前的研究表明 GIRK 亚基在小脑中有高表达，但它们的功能作用从未被清楚描述。我们使用在小鼠小脑切片上的膜片钳记录，研究了 GIRK 电流在浦肯野细胞 (PC) 中的特性，并研究了 GIRK1 包含通道的选择性激动剂 ML297 (ML) 对 PC 放电和突触可塑性的影响。我们证明 GIRK 通道的激活通过抑制钠和钙峰来降低 PC 的兴奋性，并且还调节由 climbing fiber 刺激引起的复杂 spike 反应。我们的结果表明，GIRK 通道对平行纤维-PC 突触的突触可塑性也有显著影响，因为 ML297 的应用增加了 LTP 的表达，同时防止了 LTD。因此，我们提出 GIRK 通道的募集代表了一种关键机制，通过该机制，神经调质可以控制突触强度和膜电导，以适当细化参与记忆存储和更高认知功能的神经网络。
