| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: sappel{at}uic.edu.
M-current (IM) 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 IM in acutely dissociated rat DA VTA neurons with nystatin-perforated patch recording. The standard deactivation protocol was used to measure IM during voltage-clamp recording with hyperpolarizing voltage steps to -65 mV (in 10 mV increments) from a holding potential of -25 mV. IM amplitude was voltage-dependent and maximal current amplitude was detected at -45 mV. The deactivation time constant of IM was voltage-dependent and became shorter at more negative voltages. The IM / KCNQ antagonist XE991 (0.3-30 µM) caused a concentration-dependent reduction in IM amplitude with an IC50 of 0.71 µM. Tetraethylammonium (TEA) (0.3-10 mM) caused a concentration-dependent inhibition of IM 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 without affecting the middle component of the afterhyperpolarization. Action potential amplitude, duration and threshold were not affected by XE991. In addition, 10 µM XE991 significantly shortened the inter-spike intervals in evoked spike trains. In conclusion, IM 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 afterhyperpolarization and may decrease excitability of these neurons.
This article has been cited by other articles:
|
|
 |
|
  Z. M. Khaliq and B. P. Bean Dynamic, Nonlinear Feedback Regulation of Slow Pacemaking by A-Type Potassium Current in Ventral Tegmental Area Neurons J. Neurosci., October 22, 2008; 28(43): 10905 - 10917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. Hansen, O. Waroux, V. Seutin, T. J. Jentsch, S. Aznar, and J. D. Mikkelsen Kv7 channels: interaction with dopaminergic and serotonergic neurotransmission in the CNS J. Physiol., April 1, 2008; 586(7): 1823 - 1832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yoshida and A. Alonso Cell-Type Specific Modulation of Intrinsic Firing Properties and Subthreshold Membrane Oscillations by the M(Kv7)-Current in Neurons of the Entorhinal Cortex J Neurophysiol, November 1, 2007; 98(5): 2779 - 2794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Koyama, M. S. Brodie, and S. B. Appel Ethanol Inhibition of M-Current and Ethanol-Induced Direct Excitation of Ventral Tegmental Area Dopamine Neurons J Neurophysiol, March 1, 2007; 97(3): 1977 - 1985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Appel, L. Wise, J. McDaid, S. Koyama, M. A. McElvain, and M. S. Brodie The Effects of Long Chain-Length n-Alcohols on the Firing Frequency of Dopaminergic Neurons of the Ventral Tegmental Area J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1137 - 1145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Hansen, C. Ebbesen, C. Mathiesen, P. Weikop, L. C. Ronn, O. Waroux, J. Scuvee-Moreau, V. Seutin, and J. D. Mikkelsen The KCNQ Channel Opener Retigabine Inhibits the Activity of Mesencephalic Dopaminergic Systems of the Rat J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1006 - 1019. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
