A Persistent Na⁺Current and Its Contribution to Burst-Like Firing 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, IL, USA [2]Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan

出　　处：《Journal of Biomedical Science and Engineering》2015年第7期429-440,共12页生物医学工程（英文）

摘　　要：The ventral tegmental area dopamine (DA VTA) neurons have the spontaneous tonic activity and an alteration of firing pattern from tonic to burst accelerates dopamine transmission more effectively in the mesoaccumbal dopaminergic system, leading to the reinforcing process of drugs of abuse such as alcohol and nicotine. In the present study, we examined whether a persistent Na+ current would contribute to burst firing in DA VTA neuronsusing nystatin-perforated recording. Tetrodotoxin (TTX) (1 μM) or riluzole (10 μM) hyperpolarized the membrane potential and stopped spontaneous firing of DA VTA neurons. In voltage-clamp analysis, a TTX and riluzole-sensitive and persistent Na+ current was activated at ?60 mV and reached maximal amplitude at ?40 mV. This persistent Na+ current was potentiated by a negative shift of the voltage of activation by eliminating Ca2+ from the extracellular solution. The Ca2+-free extracellular solution depolarized the membrane potential and increased the firing frequency of DA VTA neurons. When a continuous hyperpolarizing current was injected, the firing pattern of the DA VTA neurons transformed into burst-like firing;with average spike number of 4.9, average inter-spike interval of 221 ms, and an average plateau potential, on which the train of spikes generated, was 11 mV. The burst-like firing of DA VTA neurons was abolished by 10 μM riluzole. The concurrent blockade of both T-type Ca2+ current and small conductance Ca2+-activated K+(SK) currents by 100 μM nickel did not induce burst-like firing with or without continuous hyperpolarizing current injection in DA VTA neurons. In conclusion, increases in a persistent Na+ current that mediates a depolarizing driving force by removing extracellular Ca2+ contributes to burst-like firing in DA VTA neurons.The ventral tegmental area dopamine (DA VTA) neurons have the spontaneous tonic activity and an alteration of firing pattern from tonic to burst accelerates dopamine transmission more effectively in the mesoaccumbal dopaminergic system, leading to the reinforcing process of drugs of abuse such as alcohol and nicotine. In the present study, we examined whether a persistent Na+ current would contribute to burst firing in DA VTA neuronsusing nystatin-perforated recording. Tetrodotoxin (TTX) (1 μM) or riluzole (10 μM) hyperpolarized the membrane potential and stopped spontaneous firing of DA VTA neurons. In voltage-clamp analysis, a TTX and riluzole-sensitive and persistent Na+ current was activated at ?60 mV and reached maximal amplitude at ?40 mV. This persistent Na+ current was potentiated by a negative shift of the voltage of activation by eliminating Ca2+ from the extracellular solution. The Ca2+-free extracellular solution depolarized the membrane potential and increased the firing frequency of DA VTA neurons. When a continuous hyperpolarizing current was injected, the firing pattern of the DA VTA neurons transformed into burst-like firing;with average spike number of 4.9, average inter-spike interval of 221 ms, and an average plateau potential, on which the train of spikes generated, was 11 mV. The burst-like firing of DA VTA neurons was abolished by 10 μM riluzole. The concurrent blockade of both T-type Ca2+ current and small conductance Ca2+-activated K+(SK) currents by 100 μM nickel did not induce burst-like firing with or without continuous hyperpolarizing current injection in DA VTA neurons. In conclusion, increases in a persistent Na+ current that mediates a depolarizing driving force by removing extracellular Ca2+ contributes to burst-like firing in DA VTA neurons.

关 键 词：APAMIN Acutely Dissociated Neurons EXTRACELLULAR Ca2+ Nickel NYSTATIN Perforated Patch Recording 

分 类 号：R73[医药卫生—肿瘤]