title: β-Adrenergic receptor agonist increases voltage-gated Na(+) currents in medial prefrontal cortex pyramidal neurons.
abstract: The prefrontal cortex does not function properly in neuropsychiatric diseases and during chronic stress. The aim of this study was to test the effects of isoproterenol, a β-adrenergic receptor agonist, on the voltage-dependent fast-inactivating Na(+) currents in medial prefrontal cortex (mPFC) pyramidal neurons obtained from young rats. The recordings were performed in the cell-attached configuration. Isoproterenol (2μM) did not change the peak Na(+) current amplitude but shifted the IV curve of the Na(+) currents toward hyperpolarization. Pretreatment of the cells with the β-adrenergic antagonists propranolol and metoprolol abolished the effect of isoproterenol on the Na(+) currents, suggesting the involvement of β1-adrenergic receptors. The effect of β-adrenergic receptor stimulation on the sodium currents was dependent on kinase A and kinase C; the effect was diminished in the presence of the kinase A antagonist H-89 and the kinase C antagonist chelerythrine and abolished when the antagonists were coapplied. Moreover, isoproterenol depolarized the membrane potential recorded using the perforated-patch method, and this depolarization was abolished by cesium ions. Thus, in mPFC pyramidal neurons, stimulation of β-adrenergic receptors up-regulates the fast-inactivating voltage-gated Na(+) currents evoked by suprathreshold depolarizations.
authors: Department of Drug Technology and Pharmaceutical Biotechnology, The Medical University of Warsaw, Poland; Department of Physiology and Pathophysiology, CEPT, The Medical University of Warsaw, Poland. Electronic address: bartlomiej.szulczyk@wum.edu.pl.
authors: Bartlomiej
authors: B
authors: Szulczyk
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008790:Metoprolol / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D061566:Voltage-Gated Sodium Channels; D011433:Propranolol; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D008790:Metoprolol; D007545:Isoproterenol
keywords: Cell-attached; Isoproterenol; Medial prefrontal cortex; Na(+) currents; Protein kinase; β-Adrenergic receptors