TY - JOUR
T1 - The prostacyclin analogue carbacyclin inhibits Ca2+-activated K+ current in aortic baroreceptor neurones of rats
AU - Li, Zhi
AU - Lee, Hon Chi
AU - Bielefeldt, Klaus
AU - Chapleau, Mark W.
AU - Abboud, Francois M.
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1469-7793.1997.275bn.x
DO - 10.1111/j.1469-7793.1997.275bn.x
M3 - Article
C2 - 9192300
AN - SCOPUS:0030949312
SN - 0022-3751
VL - 501
SP - 275
EP - 287
JO - Journal of Physiology
JF - Journal of Physiology
IS - 2
ER -