Activation of locus coeruleus (LC) neurones by cholera toxin: mediation by cAMP-dependent protein kinase.
There is evidence that the tonic pacemaker activity of the noradrenergic pacemaker neurones of the locus coeruleus (LC) depends on endogenous cAMP acting via protein kinase A and its phosphorylation pathway. In this study, we tested the effect of cholera toxin, which produces persistent activation of Gs, on LC firing rates. Bath applied cholera toxin (holotoxin) increased LC firing rates after a lag of 50-110 min. Intracellularly applied A-subunit (active-subunit) but not the B-subunit (binding-subunit) of cholera toxin via low resistance patch electrodes mimicked the excitatory actions of bath-applied holotoxin but without its lag period. The effects of both bath-applied and intracellularly applied cholera toxin A-subunit were blocked by intracellular applications of a specific cAMP-dependent protein kinase inhibitor (PKI5-24). We conclude that persistent activation of Gs by cholera toxin (A-subunit) increases LC firing rates via the cAMP-dependent protein phosphorylation pathway.
Alreja
M
M
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508.
Aghajanian
G K
GK
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D008125:Locus Coeruleus / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D010507:Periodicity; D010766:Phosphorylation; D011480:Protease Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D015290:Second Messenger Systems; D013268:Stimulation, Chemical
D010446:Peptide Fragments; D011480:Protease Inhibitors; D047428:Protein Kinase Inhibitors; C518603:protein kinase inhibitor peptide (5-24); D002772:Cholera Toxin; D000242:Cyclic AMP; D011494:Protein Kinases; D019204:GTP-Binding Proteins