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Characterization of M-Current in Ventral Tegmental Area Dopamine Neurons

Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, Illinois

Submitted 2 June 2005; accepted in final form 27 December 2005

M-current (I_M) is a voltage-gated potassium current (KCNQ type) that affects neuronal excitability and is modulated by some drugs of abuse. Ventral tegmental area (VTA) dopamine (DA) neurons are important for the reinforcing effects of drugs of abuse. Therefore we studied I_M in acutely dissociated rat DA VTA neurons with nystatin-perforated patch recording. The standard deactivation protocol was used to measure I_M during voltage-clamp recording with hyperpolarizing voltage steps to –65 mV (in 10-mV increments) from a holding potential of –25 mV. I_M amplitude was voltage dependent and maximal current amplitude was detected at –45 mV. The deactivation time constant of I_M was voltage dependent and became shorter at more negative voltages. The I_M/KCNQ antagonist XE991 (0.3–30 µM) caused a concentration-dependent reduction in I_M amplitude with an IC₅₀ of 0.71 µM. Tetraethylammonium (TEA, 0.3–10 mM) caused a concentration-dependent inhibition of I_M with an IC₅₀ of 1.56 mM. In current-clamp recordings, all DA VTA neurons were spontaneously active. Analysis of evoked action potential shape indicated that XE991 (1–10 µM) reduced the fast and slow components of the spike afterhyperpolarization (AHP) without affecting the middle component of the AHP. Action potential amplitude, duration, and threshold were not affected by XE991. In addition, 10 µM XE991 significantly shortened the interspike intervals in evoked spike trains. In conclusion, I_M is active near threshold in DA VTA neurons, is blocked by XE991 (10 µM) and TEA (10 mM), may contribute to the shape of the AHP, and may decrease excitability of these neurons.

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