title: Stimulation of α1-adrenoceptors facilitates GABAergic transmission onto pyramidal neurons in the medial prefrontal cortex.
abstract: Whereas activation of α1-adrenoceptors (α1-ARs) modulates glutamatergic transmission, the roles of α1-ARs in GABAergic transmission in the medial prefrontal cortex (mPFC) are elusive. Here, we examined the effects of the α1-AR agonist phenylephrine (Phe) on GABAergic transmission onto pyramidal neurons in the deep layers of the mPFC. We found that bath application of Phe dose-dependently increased the amplitude of evoked IPSCs (eIPSCs). Phe increased the frequency but not the amplitude of miniature IPSCs (mIPSCs). Ca(2+) influx through T-type voltage-gated calcium channels is required for Phe-induced increases in GABA release. Phe increases GABA release probability and the number of releasable vesicles. Phe depolarizes the fast-spiking (FS) interneurons without effects on the firing rate of action potentials (APs) of interneurons. Phe-induced depolarization is independent of extracellular Na(+), Ca(2+) and T-type calcium channels, but requires inward rectifier K(+) channels (Kirs). The present study demonstrates that Phe enhances GABAergic transmission onto mPFC pyramidal neurons through inhibiting interneurons Kirs, which further depolarizes interneurons leading to increase in Ca(2+) influx via T-type calcium channels. Our results may provide a cellular and molecular mechanism that helps explain α1-AR-induced PFC dysfunction.
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China. Electronic address: luofei@ncu.edu.cn.
authors.forename: F
authors.initials: F
authors.lastname: Luo
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
authors.forename: H
authors.initials: H
authors.lastname: Tang
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
authors.forename: Z-Y
authors.initials: ZY
authors.lastname: Cheng
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D046509:Tissue Culture Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D020747:Calcium Channels, T-Type; D024661:Potassium Channels, Inwardly Rectifying; D018340:Receptors, Adrenergic, alpha-1; D015222:Sodium Channels; D010656:Phenylephrine; D005680:gamma-Aminobutyric Acid; D002118:Calcium
keywords: GABAergic transmission; medial prefrontal cortex; rat; α(1)-adrenoceptor