Noradrenergic modulation of the hyperpolarization-activated cation current (Ih) in dopamine neurons of the ventral tegmental area.
Enviado por Francisco Mariano Arencibia-Albi... el
Título | Noradrenergic modulation of the hyperpolarization-activated cation current (Ih) in dopamine neurons of the ventral tegmental area. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Autores | Arencibia-Albite, F, Paladini, C, Williams, JT, Jiménez-Rivera, CA |
Journal | Neuroscience |
Volume | 149 |
Issue | 2 |
Pagination | 303-14 |
Date Published | 2007 Oct 26 |
ISSN | 0306-4522 |
Palabras clave | Adrenergic alpha-Antagonists, Algorithms, Animals, Barium Compounds, Chlorides, Cyclic Nucleotide-Gated Cation Channels, Data Interpretation, Statistical, Dopamine, Dopamine Antagonists, Electrophysiology, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Male, Membrane Potentials, Neurons, Norepinephrine, Patch-Clamp Techniques, Potassium Channels, Prazosin, Rats, Rats, Sprague-Dawley, Receptors, Adrenergic, alpha, Receptors, Dopamine D2, Salicylamides, Ventral Tegmental Area, Yohimbine |
Abstract | Alterations in the state of excitability of midbrain dopamine (DA) neurons from the ventral tegmental area (VTA) may underlie changes in the synaptic plasticity of the mesocorticolimbic system. Here, we investigated norepinephrine's (NE) regulation of VTA DA cell excitability by modulation of the hyperpolarization-activated cation current, Ih, with whole cell recordings in rat brain slices. Current clamp recordings show that NE (40 microM) hyperpolarizes spontaneously firing VTA DA cells (11.23+/-4 mV; n=8). In a voltage clamp, NE (40 microM) induces an outward current (100+/-24 pA; n=8) at -60 mV that reverses at about the Nernst potential for potassium (-106 mV). In addition, NE (40 microM) increases the membrane cord conductance (179+/-42%; n=10) and reduces Ih amplitude (68+/-3% of control at -120 mV; n=10). The noradrenergic alpha-1 antagonist prazosin (40 microM; n=5) or the alpha-2 antagonist yohimbine (40 microM; n=5) did not block NE effects. All NE-evoked events were blocked by the D2 antagonists sulpiride (1 microM) and eticlopride (100 nM) and no significant reduction of Ih took place in the presence of the potassium channel blocker BaCl2 (300 microM). Therefore, it is concluded that NE inhibition of Ih was due to an increase in membrane conductance by a nonspecific activation of D2 receptors that induce an outward potassium current and is not a result of a second messenger system acting on h-channels. The results also suggest that Ih channels are mainly located at dendrites of VTA DA cells and, thus, their inhibition may facilitate the transition from single-spike firing to burst firing and vice versa. |
DOI | 10.1016/j.neuroscience.2007.08.009 |
Alternate Journal | Neuroscience |
PubMed ID | 17884297 |
PubMed Central ID | PMC2254936 |
Grant List | GM-08224 / GM / NIGMS NIH HHS / United States GM-50695 / GM / NIGMS NIH HHS / United States NS39408 / NS / NINDS NIH HHS / United States S06 GM008224-18 / GM / NIGMS NIH HHS / United States S06 GM050695 / GM / NIGMS NIH HHS / United States S06 GM050695-080018 / GM / NIGMS NIH HHS / United States U54 NS039408 / NS / NINDS NIH HHS / United States U54 NS039408-040003 / NS / NINDS NIH HHS / United States U54 NS039408-05 / NS / NINDS NIH HHS / United States |