Author(s)

Susumu Koyama^1,2*, Munechika Enjoji², Mark S. Brodie¹, Sarah B. Appel¹

¹Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, USA.
¹Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, USA.
²Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.

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 (I_M) 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 I_M and the spontaneous firing frequency of DA VTA neurons. The standard deactivation protocol was used to measure I_M during voltage-clamp recording with a hyperpolarizing voltage step to ﹣40 mV from a holding potential (V_H) of ﹣25 mV. Zn²⁺ (100 μM) inhibited I_M amplitude and I_M recovered completely from the inhibition after the washout of Zn2+. Zn2+ inhibited I_M in a concentration-dependent manner (IC50: 5.8 μM). When hyperpolarizing voltage steps were given to ﹣65 mV (in 10 mV increments) from a V_H 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 I_M. I_M of DA VTA neurons was inhibited by 100 μM divalent cations in increasing order of potency: Ba²⁺ (16%) < Co²⁺ (25%) < Ni²⁺ (40%) < Cd²⁺ (59%) < Zn²⁺ (67%). These results suggest that Zn²⁺ may exert physiologically significant regulation of neuronal excitability in DA VTA neurons.

Divalent Cation, Dopaminergic, Nystatin-Perforated Patch Recording, Zinc

Koyama, S. , Enjoji, M. , Brodie, M. and Appel, S. (2014) The Effects of Zinc and Other Divalent Cations on M-Current in Ventral Tegmental Area Dopamine Neurons. Journal of Biomedical Science and Engineering, 7, 1075-1087. doi: 10.4236/jbise.2014.714105.