title: Pacemaker activity of locus coeruleus neurons: whole-cell recordings in brain slices show dependence on cAMP and protein kinase A.
abstract: Noradrenergic neurons of the rat locus coeruleus (LC) are endogenous pacemakers that exhibit slow, tonic firing even in the complete absence of synaptic inputs. In the present study a time-dependent decline in LC spontaneous firing activity was found on intracellular dialysis during whole-cell recording with low-resistance patch electrodes; this decline was accentuated by a specific inhibitor of cAMP-dependent protein kinase (PKI5-24). Conversely, the inclusion of cAMP, 8-Br-cAMP, or the catalytic subunit of cAMP-dependent protein kinase (PKAcat) in the patch pipettes dose-dependently increased firing rate; intracellular PKI5-24 blocked both 8-Br-cAMP and PKAcat-induced firing in LC neurons. These results indicate that endogenous cAMP, via a phosphorylation-dependent route, drives tonic pacemaker activity in LC neurons.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508.
authors.forename: M
authors.initials: M
authors.lastname: Alreja
authors.forename: G K
authors.initials: GK
authors.lastname: Aghajanian
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology*; D003956:Dialysis; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010507:Periodicity; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000494:pharmacology*; D051381:Rats
chemical_list: D047428:Protein Kinase Inhibitors; D000242:Cyclic AMP; D011494:Protein Kinases