D(1) dopaminergic control of G protein-dependent inward rectifier K(+) (GIRK)-like channel current in pyramidal neurons of the medial prefrontal cortex.
Pyramidal neurons of the medial prefrontal cortex (mPFC) exhibit dopamine-dependent prolonged depolarization, which may lead to persistent activity. Persistent activation of prefrontal cortex neurons has been proposed to underlie the working memory process. The purpose of our study was to test the hypothesis that activation of D(1) dopamine receptors leads to inhibition of G protein-dependent inward rectifier K(+) (GIRK) channels, thereby supporting the prolonged depolarization of mPFC pyramidal neurons. Experiments were performed on 3-week-old rats. GIRK-like channel currents recorded from pyramidal neurons showed the following properties at -75 mV: open probability (NPo), 2.5+/-0.3 x 10(-3); mean open time, 0.53+/-0.05 ms; and conductance, 29.9+/-1.6 pS (n=60). The channel currents were strongly inward-rectified. GIRK channel currents were reversibly inhibited by the D(1) agonists SKF 38393 (10 microM) and SKF 81297 (10 microM). This inhibition was abolished by prior application of a dopamine receptor antagonist and by application of the membrane-permeable protein kinase C inhibitors chelerythrine chloride (3 microM) and calphostin C (10 microM). It was also found that the application of D(1) dopamine receptor agonists or GIRK channel inhibitors evoked depolarization of mPFC pyramidal neurons in rats. Moreover, prior application of a GIRK channel blocker eliminated the depolarizing effect of D(1) agonists. We conclude that activation of D(1) dopamine receptors may lead to inhibition of GIRK channel currents that may, in turn, lead to the prolonged depolarization of mPFC pyramidal neurons in juvenile rats.
Department of Physiology, The Medical University of Warsaw, Krakowskie Przedmiescie 26/28, Warsaw, Poland.
G
G
Witkowski
B
B
Szulczyk
R
R
Rola
P
P
Szulczyk
D000704:Analysis of Variance; D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D001514:Bee Venoms; D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D009281:Naphthalenes; D026902:Potassium Channel Blockers; D017447:Receptors, Dopamine D1; C061465:calphostin complex; C029738:tertiapin; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D013755:Tetradecanoylphorbol Acetate