ACTIVATION OF ADENYLATE-CYCLASE ATTENUATES THE HYPERPOLARIZATION FOLLOWING SINGLE ACTION-POTENTIALS IN BRAIN NORADRENERGIC - NEURONS INDEPENDENTLY OF PROTEIN-KINASE-A

Citation
R. Shiekhattar et G. Astonjones, ACTIVATION OF ADENYLATE-CYCLASE ATTENUATES THE HYPERPOLARIZATION FOLLOWING SINGLE ACTION-POTENTIALS IN BRAIN NORADRENERGIC - NEURONS INDEPENDENTLY OF PROTEIN-KINASE-A, Neuroscience, 62(2), 1994, pp. 523-529
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
0306-4522
Volume
62
Issue
2
Year of publication
1994
Pages
523 - 529
Database
ISI
SICI code
0306-4522(1994)62:2<523:AOAATH>2.0.ZU;2-M
Abstract
Afterhyperpolarizations that follow action potentials are a prominent mechanism for the control of neuronal excitability. Such afterhyperpol arizations in many neurons are modulated by a variety of second messen ger systems. Here, we examined the regulation of afterhyperpolarizatio ns in noradrenergic locus coeruleus neurons by the adenylate cyclase s ystem. Although superfusion of the adenylate cyclase activator, forsko lin, had no effect on hyperpolarizations following trains of action po tentials, both forskolin and a membrane permeable analog of cyclic AMP , 8-bromo-cyclic AMP, attenuated the amplitude of afterhyperpolarizati ons which followed single action potentials of locus coeruleus neurons recorded intracellularly in brain slices. In contrast, superfusion of 1,9-dideoxyforskolin, the forskolin analog that does not activate ade nylate cyclase, had no effect on these single action potential afterhy perpolarizations. Co-application of a protein kinase inhibitor (H8, KT 5720, staurosporin or Rp-cAMPS) with either forskolin or 8-bromo-cycli c AMP failed to block the reduction of afterhyperpolarization amplitud e, but blocked the cyclic AMP-dependent enhancement of opiate response s in the same locus coeruleus neurons. Furthermore, application of a m embrane permeable analog of 5'-AMP, 8-bromo-5'-AMP, the cyclic AMP met abolite that does not activate a protein kinase, potently reduced the amplitudes of single action potential afterhyperpolarizations. The aft erhyperpolarization amplitude was also reduced in locus coeruleus neur ons taken from chronically morphine-treated rats, a treatment known to increase adenylate cyclase activity. These results indicate that elev ation of intracellular cyclic AMP or 5'-AMP reduces the single action potential afterhyperpolarization in locus coeruleus neurons. This acti on may be mediated through a mechanism independent of protein kinase a ctivation.