Dopamine D1/D5 receptor activation modulates a persistent sodium current in rat prefrontal cortical neurons in vitro.
The effects of dopamine (DA) on a persistent Na(+) current (I(NaP)) in layer V-VI prefrontal cortical (PFC) pyramidal cells were studied using whole cell voltage-clamp recordings in rat PFC slices. After blocking K(+) and Ca (2+) currents, a tetrodotoxin-sensitive I(NaP) was activated by slow depolarizing voltage ramps or voltage steps. DA modulated the I(NaP) in a voltage-dependent manner: increased amplitude of I(NaP) at potentials more negative than -40 mV, but decreased at more positive potentials. DA also slowed the inactivation process of I(NaP). The D1/D5 dopamine receptor agonists SKF 38393, SKF 81297, and dihydrexidine (3-10 microM), but not the dopamine D2/D3 receptor agonist qiunpirole (1-20 microM), mimicked the effects of DA on I(NaP). Modulation of I(NaP) by D1/D5 agonists was blocked by the D1/D5 antagonist SCH23390. Bath application of specific protein kinase C inhibitor, chelerhythrine, or inclusion of the specific protein kinase C inhibiting peptide([19-36]) in the recording pipette, but not protein kinase A inhibiting peptide([5-24]), blocked the effect of D1/D5 agonists on I(NaP). In current-clamp recordings, D1/D5 receptors activation enhanced the excitability of cortical pyramidal cells. Application of the D1/D5 agonist SKF 81297 induced a long-lasting decrease in the first spike latency in response to depolarizing current ramp. This was associated with a shift in the start of nonlinearity in the slope resistance to more negative membrane potentials. We proposed that this effect is due to a D1/D5 agonist-induced leftward shift in the activation of I(NaP). This enables DA to facilitate the firing of PFC neurons in response to depolarizing inputs.
Gorelova
N A
NA
Department of Psychology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
Yang
C R
CR
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000470:Alkaloids; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D053119:Benzophenanthridines; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010617:Phenanthridines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology* / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017966:Pyramidal Cells / Q000737:chemistry / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D050641:Receptors, Dopamine D5; D012964:Sodium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D000470:Alkaloids; D001552:Benzazepines; D053119:Benzophenanthridines; D018491:Dopamine Agonists; C493607:Drd5 protein, rat; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5; C061532:dihydrexidine; D013779:Tetrodotoxin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C067113:SK&F 81297; D012964:Sodium; C016299:chelerythrine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D004298:Dopamine