Ghrelin, a 28 amino acid brain-gut peptide, has attracted increasing attention for its neuroprotective effect in Parkinson's disease (PD). In view of the pivotal role of excitability of dopaminergic neurons in substantia nigra pars compacta (SNc) in the function of nigrostriatal system, it is of great significance to elucidate the regulation of electrical activity of dopaminergic neurons by ghrelin, especially in PD pathogenesis. In this study, we tackled this issue by probing the effects of ghrelin on the electrophysiological properties of dopaminergic neurons in acute application of Methyl-4-phenylpyridinium (MPP⁺), a potent parkinsonizing agent in primates and rodents, with whole cell patch clamp technique. We first observed that MPP⁺ (10, 20 and 50 μM) inhibited the spontaneous firing activity of dopaminergic neurons with dose-dependent and time-dependent properties. MPP⁺ also hyperpolarized the membrane potential, inhibited the evoked firing activity and reduced the amplitude of the inward rectification characteristic (Sag) in dopaminergic neurons. Importantly, ghrelin (100 nM) could improve the above effects of MPP⁺ on the electrical activities of dopaminergic neurons. The potential mechanism of this phenomenon may be that ghrelin upregulated hyperpolarization-activated cyclic nucleotide-gated channel current (I_h) to antagonize the inhibition of MPP⁺ on I_h, thereby improving the electrical activities of dopaminergic neurons.

Ghrelin 是一种 28 氨基酸的脑肠肽，因其对帕金森病 (PD) 的神经保护作用而受到越来越多的关注。鉴于黑质致密部（SNc）多巴胺能神经元兴奋性在黑质纹状体系统功能中的关键作用，阐明ghrelin对多巴胺能神经元电活动的调节，特别是在PD发病机制中具有重要意义。在这项研究中，我们通过甲基-4-苯基（MPP急性应用探测多巴胺能神经元的电生理特性生长素的作用解决这一问题⁺），在灵长类动物和啮齿类动物的有力parkinsonizing剂，用全细胞膜片钳技术. 我们首先观察到 MPP ⁺(10、20 和 50 μM) 抑制多巴胺能神经元的自发放电活动，具有剂量依赖性和时间依赖性。MPP ⁺还使膜电位超极化，抑制诱发的放电活动并降低多巴胺能神经元的内向整流特征 (Sag) 的幅度。重要的是，ghrelin (100 nM) 可以改善 MPP ⁺对多巴胺能神经元电活动的上述影响。这种现象的潜在机制可能是ghrelin通过上调超极化激活的环核苷酸门控通道电流（I _h）来拮抗MPP ⁺对I _h的抑制作用。，从而改善多巴胺能神经元的电活动。