title: Dopaminergic modulation of GABAergic transmission in the entorhinal cortex: concerted roles of α1 adrenoreceptors, inward rectifier K⁺, and T-type Ca²⁺ channels.
abstract: Whereas the entorhinal cortex (EC) receives profuse dopaminergic innervations from the midbrain, the effects of dopamine (DA) on γ-Aminobutyric acid (GABA)ergic interneurons in this brain region have not been determined. We probed the actions of DA on GABAA receptor-mediated synaptic transmission in the EC. Application of DA increased the frequency, not the amplitude, of spontaneous IPSCs (sIPSCs) and miniature IPSCs (mIPSCs) recorded from entorhinal principal neurons, but slightly reduced the amplitude of the evoked IPSCs. The effects of DA were unexpectedly found to be mediated by α1 adrenoreceptors, but not by DA receptors. DA endogenously released by the application of amphetamine also increased the frequency of sIPSCs. Ca(2+) influx via T-type Ca(2+) channels was required for DA-induced facilitation of sIPSCs and mIPSCs. DA depolarized and enhanced the firing frequency of action potentials of interneurons. DA-induced depolarization was independent of extracellular Na(+) and Ca(2+) and did not require the functions of hyperpolarization-activated (Ih) channels and T-type Ca(2+) channels. DA-generated currents showed a reversal potential close to the K(+) reversal potential and inward rectification, suggesting that DA inhibits the inward rectifier K(+) channels (Kirs). Our results demonstrate that DA facilitates GABA release by activating α1 adrenoreceptors to inhibit Kirs, which further depolarize interneurons resulting in secondary Ca(2+) influx via T-type Ca(+) channels.
authors.affiliation: Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Cilz
authors.affiliation: Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
authors.forename: Lalitha
authors.initials: L
authors.lastname: Kurada
authors.affiliation: Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
authors.forename: Binqi
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
authors.forename: Saobo
authors.initials: S
authors.lastname: Lei
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D018728:Entorhinal Cortex / Q000166:cytology*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D020748:Mibefradil / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D002614:Chelating Agents; D018377:Neurotransmitter Agents; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D018340:Receptors, Adrenergic, alpha-1; D020748:Mibefradil; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D004298:Dopamine
keywords: GABAA receptor; depolarization; entorhinal; interneuron; synapse; synaptic transmission