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The Prostacyclin Analogue Carbacyclin Inhibits Ca2+‐Activated K+ Current in Aortic Baroreceptor Neurones of Rats
Journal article   Open access   Peer reviewed

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 and Francois M Abboud
The Journal of physiology, Vol.501(2), pp.275-287
06/1997
DOI: 10.1111/j.1469-7793.1997.275bn.x
PMID: 9192300
url
https://doi.org/10.1111/j.1469-7793.1997.275bn.xView
Published (Version of record) Open Access

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 (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 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. 4 Carbacyclin‐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. 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.

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