Activation of alpha1-adrenoceptors increases firing frequency through protein kinase C in pyramidal neurons of rat visual cortex.
Properties of repetitive firing, including spike adaptation, are considered to play an essential role in controlling neural excitability in the central nervous system. Noradrenaline is one of major neurotranmitters that modulate repetitive firing in the cerebral cortex. Although activation of beta-adrenoceptors increases firing frequency similarly to noradrenaline, it is still controversial whether alpha(1)-adrenoceptor activation influences repetitive firing. In the present study, we examined the effects of adrenoceptor agonists on firing properties and the intracellular mechanism for alpha(1)-adrenoceptor-dependent modulation of firing in pyramidal neurons of rat cerebral cortex. In agreement with previous reports, bath application of 100microM isoproterenol, a beta-adrenoceptor agonist, increased firing frequency in response to a long intracellular depolarizing current injection. Phenylephrine (100microM), an alpha(1)-adrenoceptor agonist, also increased firing rate, which was inhibited by 100microM prazosin, an alpha1-adrenoceptor antagonist. The extent of increment in firing rate is comparable to that induced by isoproterenol. Furthermore, phenylephrine's effects on firing properties were mimicked by 2-5microM phorbol ester, a protein kinase C (PKC) activator, and pre-application of 10microM chelerythrine, a PKC inhibitor, prevented phenylephrine-induced facilitation of repetitive firing. These results suggest that phenylephrine has a facilitatory effect on repetitive firing through PKC activation.
Kobayashi
Masayuki
M
Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan. kobayashi-ms@dent.nihon-u.ac.jp
Sasabe
Tetsuya
T
Shiohama
Yasuteru
Y
Koshikawa
Noriaki
N
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D009431:Neural Conduction / Q000187:drug effects / Q000528:radiation effects; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013997:Time Factors; D014793:Visual Cortex / Q000166:cytology*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D011493:Protein Kinase C; C013411:biocytin; D008239:Lysine; D007545:Isoproterenol