The prostacyclin analogue carbacyclin inhibits Ca2+-activated K+ current in aortic baroreceptor neurones of rats

Zhi Li, Hon Chi Lee, Klaus Bielefeldt, Mark W. Chapleau, Francois M. Abboud

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

1. Previous studies indicate that prostacyclin (PGI2,) increases the activity of baroreceptor afferent fibres. The purpose of this study was to test the hypothesis that PGI2 inhibits Ca2+-activated K+ current (I(K(Ca))) in isolated baroreceptor neurones in culture. 2. Rat aortic baroreceptor neurones in the nodose ganglia were labelled in vivo by applying a fluorescent dye (DiI) to the aortic arch 1-2 weeks before dissociation of the neurones. Outward K+ currents in baroreceptor neurones evoked by depolarizing voltage steps from a holding potential of -40 mV were recorded using the whole-cell patch-clamp technique. 3. Exposure of baroreceptor neurones to the stable PGI2 analogue carbacyclin significantly inhibited the steady-state K+ current in a dose-dependent and reversible manner. The inhibition of K+ current was not caused indirectly by changes in cytosolic Ca2+ concentration. The Ca2+-activated K+ channel blocker charybdotoxin (ChTX, 10-7 M) also inhibited the K+ current. In the presence of ChTX or in the absence of Ca2+, carbacyclin failed to inhibit the residual K+ current. Furthermore, in the presence of high concentrations of carbacyclin, ChTX did not cause further reduction of K+ current. 4. Carbacyclin-induced inhibition of I(K(Ca)) was mimicked by 8-bromo-cAMP and by activation of G-protein with GTPγS. The inhibitory effect of carbacyclin on I(K(Ca)) was abolished by GDPβS, which blocks G-protein activation, and by a selective inhibitor of cAMP-dependent protein kinase, PKI5-24. 5. The results demonstrate that carbacyclin inhibits ChTX-sensitive I(K(Ca)) in isolated aortic baroreceptor neurones by a G-protein-coupled activation of cAMP-dependent protein kinase. This mechanism may contribute to the PGI2-induced increase in baroreceptor activity demonstrated previously.

Original languageEnglish (US)
Pages (from-to)275-287
Number of pages13
JournalJournal of Physiology
Volume501
Issue number2
DOIs
StatePublished - Jul 17 1997

ASJC Scopus subject areas

  • Physiology

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