title: Inward rectifier K+channel and T-type Ca2+channel contribute to enhancement of GABAergic transmission induced by β1-adrenoceptor in the prefrontal cortex.
abstract: The functions of prefrontal cortex (PFC) are sensitive to norepinephrine (NE). Endogenously released NE influences synaptic transmission through activation of different subtypes of adrenergic receptors in PFC including α1, α2, β1or β2-adrenoceptor. Our recent study has revealed that β1-adrenoceptor (β1-AR) activation modulates glutamatergic transmission in the PFC, whereas the roles of β1-AR in GABAergic transmission are elusive. In the current study, we probed the effects of the β1-AR agonist dobutamine (Dobu) on GABAergic transmission onto pyramidal neurons in the PFC of juvenile rats. Dobu increased both the frequency and amplitude of miniature IPSCs (mIPSCs). Ca2+influx through T-type voltage-gated Ca2+channel was required for Dobu-enhanced mIPSC frequency. We also found that Dobu facilitated GABA release probability and the number of releasable vesicles through regulating T-type Ca2+channel. Dobu depolarized GABAergic fast-spiking (FS) interneurons with no effects on the firing rate of action potentials (APs) of interneurons. Dobu-induced depolarization of FS interneurons required inward rectifier K+channel (Kir). Our results suggest that Dobu increase GABA release via inhibition of Kir, which further depolarizes FS interneurons resulting in Ca2+influx via T-type Ca2+channel.
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China. Electronic address: luofei@ncu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004280:Dobutamine / Q000494:pharmacology; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology*; D017966:Pyramidal Cells / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D018691:Excitatory Amino Acid Antagonists; D018682:GABA Agents; D024661:Potassium Channels, Inwardly Rectifying; D011810:Quinoxalines; D011941:Receptors, Adrenergic; D026941:Sodium Channel Blockers; D004280:Dobutamine; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine
keywords: GABAergic transmission; Inward rectifier K(+) channel; Prefrontal cortex; T-type calcium channel; β(1)-Adrenoceptor