Activation of locus coeruleus (LC) neurones by cholera toxin: Mediation by cAMP-dependent protein kinase

Abstract

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 G s, 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 (PKI 5–24). We conclude that persistent activation of G s by cholera toxin (A-subunit) increases LC firing rates via the cAMP-dependent protein phosphorylation pathway.