Characterization of M-Current in Ventral Tegmental Area Dopamine Neurons

Abstract

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 microM) caused a concentration-dependent reduction in I(M) amplitude with an IC(50) of 0.71 microM. Tetraethylammonium (TEA, 0.3-10 mM) caused a concentration-dependent inhibition of I(M) with an IC(50) 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 microM) 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 microM 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 microM) and TEA (10 mM), may contribute to the shape of the AHP, and may decrease excitability of these neurons.

Peptide hormone ghrelin enhances neuronal excitability by inhibition of Kv7/KCNQ channels

“…3a, left panel). The deactivation time constant was about 185 ± 18.3 ms at À 40 mV, which is comparable to that of KCNQ current recorded in dopaminergic neurons of ventral tegmental area 22 . The amplitude of KCNQ current in SNc was 20.9 ± 7.4 pA when measured at À 40 mV (n ¼ 13, Fig.…”

“…KCNQ/ M-currents in the nigral dopaminergic neurons were examined using a standard deactivation protocol 17,22,30 . Neurons were constantly held at À 20 mV to minimize contamination from currents such as A-type potassium current or sodium current.…”

“…Both Kv7/KCNQ channels and GHS-R are expressed in the SNc, hippocampus, dorsal root ganglion (DRG), hypothalamus and cortex 11,15,[17][18][19][20][21][22][23] . KCNQ channels are also negatively modulated by G-protein-coupled receptors via Gq and/ or G 11 activated phospholipase C (PLC)-mediated signal pathway [24][25][26] .…”

The Effects of Long Chain-Lengthn-Alcohols on the Firing Frequency of Dopaminergic Neurons of the Ventral Tegmental Area

“…The tip resistances of the electrodes were 1.5 to 3 M⍀ when filled with pipette solution (60 mM potassium acetate, 60 mM KCl, 1 mM CaCl 2 , 2 mM MgCl 2 , 40 mM HEPES, pH 7.2 adjusted with KOH, final [K ϩ ] i ϭ 131 mM; osmolality was adjusted to 290 mOsm with sucrose). Nystatin-perforated patch recording was used as described previously (Koyama and Appel, 2006). Current-clamp recording was done in the HEPES-buffered solution constantly bubbled with 100% O 2 .…”

A Persistent Na<sup>+</sup> Current and Its Contribution to Burst-Like Firing in Ventral Tegmental Area Dopamine Neurons

“…In current-clamp recording, nystatin-perforated patch recording was employed as previously described [8]. Microelectrodes were fabricated on a P-87 puller (Sutter Instrument Company, Novato, CA) from glass capillaries (LE16; Dagan, Minneapolis, MN) and heat-polished on a microforge (Narishige, Tokyo, Japan).…”