• 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.