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Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Through affecting the electrical properties of neurons in central nervous system, ghrelin exerts multiple effects, including appetite stimulation, energy balance modulation and neuroprotection. Our previous study showed that ghrelin increased the firing frequency of nigral dopaminergic neurons via inhibition of Kv7/KCNQ/M channels through activation of GHS-R/PLC/PKC pathway. However, whether the other potassium channels are also involved in the ghrelin-induced excitability of dopaminergic neurons still remain unclear. In this study, we focus on two voltage-gated potassium channels, the delayed rectifier potassium channels (IK) and A-type potassium channels (IA), which have a wide expression on dopaminergic neurons. Using whole-cell patch clamp recordings in vitro, our results indicated that ghrelin could reversibly inhibit IK and IA. The inhibition of IA showed an dose-dependent tendency, as the amplitude of IA decreased by 33.43% ± 3.78% and 52.92%±6.56% after 10 nM and 100 nM ghrelin treatment, respectively. These inhibitory effects of ghrelin were mediated by PKCδ system. The broad spectrum voltage-gated potassium channels blocker TEA, IA specific blocker 4-AP, and PKCδ specific blocker Rottlerin, occluded the excitatory effects of ghrelin. These results demonstrated that inhibition of IK and IA may contribute to the ghrelin-induced excitation of dopaminergic neurons. |
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Keywords:Ghrelin; A-type K channel; dopaminergic neurons |
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