Author's email address F. M. Abboud: firstname.lastname@example.org
The Prostacyclin Analogue Carbacyclin Inhibits Ca2+-Activated K+ Current in Aortic Baroreceptor Neurones of Rats
Article first published online: 30 SEP 2004
© 1997 The Physiological Society
The Journal of Physiology
Volume 501, Issue 2, pages 275–287, June 1997
How to Cite
Li, Z., Lee, H.-C., Bielefeldt, K., Chapleau, M. W. and Abboud, F. M. (1997), The Prostacyclin Analogue Carbacyclin Inhibits Ca2+-Activated K+ Current in Aortic Baroreceptor Neurones of Rats. The Journal of Physiology, 501: 275–287. doi: 10.1111/j.1469-7793.1997.275bn.x
- Issue published online: 30 SEP 2004
- Article first published online: 30 SEP 2004
- Received 16 December 1996; accepted 28 February 1997.
- 1Previous 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 (IK(Ca)) in isolated baroreceptor neurones in culture.
- 2Rat 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.
- 3Exposure 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, 10−7m) 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.
- 4Carbacyclin-induced inhibition of IK(Ca) was mimicked by 8-bromo-cAMP and by activation of G-protein with GTPγS. The inhibitory effect of carbacyclin on IK(Ca) was abolished by GDPβS, which blocks G-protein activation, and by a selective inhibitor of cAMP-dependent protein kinase, PKI5–24.
- 5The 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.