Cooperative activation of D1 and D2 dopamine receptors enhances a hyperpolarization-activated inward current in layer I interneurons.
Layer I of the neocortex comprises axonal processes from widespread regions of the brain and a unique population of GABAergic interneurons. Dopamine is known to directly depolarize layer I interneurons, but the underlying mechanism is unclear. Using whole-cell recording techniques in neocortical brain slices, we have examined how dopamine increases excitability of layer I interneurons in postnatal day 7-11 rats. Dopamine (30 microm) caused a 10 mV depolarization of layer I neurons. Paradoxically, neither the D1-like receptor agonist 6-chloro-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine hydrobromide (SKF81297) (1-10 microm) nor the D2-like agonist quinpirole (10 microm) produced a significant depolarization. Depolarization was observed when SKF81297 and quinpirole were coapplied. When G-protein betagamma subunits were included in the recording pipette, D1 but not D2 agonists depolarized layer I neurons. Bath application of 4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride, a specific blocker of inwardly rectifying hyperpolarization-activated current (Ih) channels, hyperpolarized the neurons and occluded the action of dopamine. Voltage-clamp analysis demonstrated that dopamine increased the amplitude and shifted the voltage dependence of activation of Ih. These results indicate that Ih contributes to the resting potential of layer I interneurons and is subject to modulation by dopamine.
Department of Neurobiology, Civitan International Research Center, University of Alabama, Birmingham, Alabama 35294, USA.
JianPing
J
Wu
John J
JJ
Hablitz
D000200:Action Potentials; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002412:Cations / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D017136:Ion Transport; D008564:Membrane Potentials; D019579:Neocortex / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D001552:Benzazepines; D002412:Cations; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D010446:Peptide Fragments; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C518603:protein kinase inhibitor peptide (5-24); D005576:Colforsin; D019257:Quinpirole; D005680:gamma-Aminobutyric Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine