title: The prostacyclin analogue carbacyclin inhibits Ca(2+)-activated K+ current in aortic baroreceptor neurones of rats.
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 Ca(2+)-activated K+ current (IK(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 Ca(2+)-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 IK(Ca) was mimicked by 8-bromo-cAMP and by activation of G-protein with GTP gamma S. The inhibitory effect of carbacyclin on IK(Ca) was abolished by GDP beta S, 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 IK(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.
authors.affiliation: Department of Physiology & Biophysics, University of Iowa College of Medicine, Iowa City, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: H C
authors.initials: HC
authors.lastname: Lee
authors.forename: K
authors.initials: K
authors.lastname: Bielefeldt
authors.forename: M W
authors.initials: MW
authors.lastname: Chapleau
authors.forename: F M
authors.initials: FM
authors.lastname: Abboud
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases; D004558:Electric Stimulation; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011311:Pressoreceptors / Q000187:drug effects*; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015221:Potassium Channels; D011465:Prostaglandins, Synthetic; C026678:carboprostacyclin; D011464:Epoprostenol; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D002118:Calcium