The Effects of Zinc and Other Divalent Cations on M-Current in Ventral Tegmental Area Dopamine Neurons  

作　　者：Susumu Koyama Munechika Enjoji Mark S. Brodie Sarah B. Appel 

机构地区：[1]Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, USA [1]Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, USA [2]Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan

出　　处：《Journal of Biomedical Science and Engineering》2014年第14期1075-1087,共13页生物医学工程（英文）

摘　　要：Ventral tegmental area dopamine (DA VTA) neurons are important for the reinforcing effects of drugs of abuse such as ethanol and nicotine. We have previously shown that M-current (IM) regulates the excitability of DA VTA neurons. Zinc (Zn2+) contributes to the regulation of neuronal excitation as a neuromodulator. In the present study, we investigated zinc effect on the properties of IM and the spontaneous firing frequency of DA VTA neurons. The standard deactivation protocol was used to measure IM during voltage-clamp recording with a hyperpolarizing voltage step to ﹣40 mV from a holding potential (VH) of ﹣25 mV. Zn2+ (100 μM) inhibited IM amplitude and IM recovered completely from the inhibition after the washout of Zn2+. Zn2+ inhibited IM in a concentration-dependent manner (IC50: 5.8 μM). When hyperpolarizing voltage steps were given to ﹣65 mV (in 10 mV increments) from a VH of ﹣25 mV, Zn2+ (100 μM) reduced IM amplitude at each voltage and zinc inhibition of IM was not voltage-dependent. Zn2+ increased the spontaneous firing frequency of DA VTA neurons in a concentration-dependent manner, suggesting that Zn2+ causes excitation of DA VTA neurons through an action on IM. IM of DA VTA neurons was inhibited by 100 μM divalent cations in increasing order of potency: Ba2+ (16%) 2+ (25%) 2+ (40%) 2+ (59%) 2+ (67%). These results suggest that Zn2+ may exert physiologically significant regulation of neuronal excitability in DA VTA neurons.Ventral tegmental area dopamine (DA VTA) neurons are important for the reinforcing effects of drugs of abuse such as ethanol and nicotine. We have previously shown that M-current (IM) regulates the excitability of DA VTA neurons. Zinc (Zn2+) contributes to the regulation of neuronal excitation as a neuromodulator. In the present study, we investigated zinc effect on the properties of IM and the spontaneous firing frequency of DA VTA neurons. The standard deactivation protocol was used to measure IM during voltage-clamp recording with a hyperpolarizing voltage step to ﹣40 mV from a holding potential (VH) of ﹣25 mV. Zn2+ (100 μM) inhibited IM amplitude and IM recovered completely from the inhibition after the washout of Zn2+. Zn2+ inhibited IM in a concentration-dependent manner (IC50: 5.8 μM). When hyperpolarizing voltage steps were given to ﹣65 mV (in 10 mV increments) from a VH of ﹣25 mV, Zn2+ (100 μM) reduced IM amplitude at each voltage and zinc inhibition of IM was not voltage-dependent. Zn2+ increased the spontaneous firing frequency of DA VTA neurons in a concentration-dependent manner, suggesting that Zn2+ causes excitation of DA VTA neurons through an action on IM. IM of DA VTA neurons was inhibited by 100 μM divalent cations in increasing order of potency: Ba2+ (16%) 2+ (25%) 2+ (40%) 2+ (59%) 2+ (67%). These results suggest that Zn2+ may exert physiologically significant regulation of neuronal excitability in DA VTA neurons.

关 键 词：DIVALENT CATION DOPAMINERGIC Nystatin-Perforated PATCH Recording ZINC 

分 类 号：R73[医药卫生—肿瘤]