K+ current inhibition by prostacyclin analog carbacyclin in baroreceptor neurons requires g-protein activation and CAMP formation

Z. Li, Hon Chi Lee, K. Bielefeldt, P. M. Abboud, M. W. Chapleau

Research output: Contribution to journalArticle

Abstract

Prostacyclin (PGI2) increases baroreceptor (BR) sensitivity in vivo. We have previously shown that the stable PGI2 analog carbacyclin (CC) inhibits Ca2+-activated K+ current in isolated BR neurons and the effect is blocked by a specific inhibitor of cAMP-dependent protein kinase (PKA). In this study we tested the hypothesis that the mechanism involves binding of CC to G-protein coupled receptors on BR neurons and subsequent formation of CAMP. Aortic BR neurons in nodose ganglia were labeled and identified by their uptake of fluorescent dye (Di-I) applied to adventitia of rat aortic arch 1 -2 weeks prior to dissociation of nodose neurons. Whole cell patch-clamp techniques were used to record outward K+ current elicited by 200 rrts voltage step from -60 to +40 mV. CC (0.1 mM) inhibited outward K current to 64±4% of control (n=8, p<0.01)- Replacing GTP in (he intracellular (pipette) solution with GDP-β-S (0.5 mM) to prevent Gprotein activation abolished CC-induced inhibition of the K+ current (n=4). The inhibitory effect of CC was mimicked by direct activation of G-proteins with intracellular application of GTP-γ-S (n=3). Exposure of BR neurons to the membrane permeable cAMP analog 8-bromo-cAMP (1-5 mM) inhibited the K+ current significantly (n=6). These results indicate thai CC-induccd inhibition of K+ current in BR neurons is mediated by activation of a G-protein and cAMP/PKA pathway.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996
Externally publishedYes

Fingerprint

prostacyclin
Pressoreceptors
Epoprostenol
Neurons
neurons
Chemical activation
Proteins
proteins
Guanosine Triphosphate
G-proteins
GTP-Binding Proteins
Nodose Ganglion
8-Bromo Cyclic Adenosine Monophosphate
Adventitia
patch-clamp technique
cAMP-dependent protein kinase
fluorescent dyes
Clamping devices
Arches
Patch-Clamp Techniques

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

K+ current inhibition by prostacyclin analog carbacyclin in baroreceptor neurons requires g-protein activation and CAMP formation. / Li, Z.; Lee, Hon Chi; Bielefeldt, K.; Abboud, P. M.; Chapleau, M. W.

In: FASEB Journal, Vol. 10, No. 3, 1996.

Research output: Contribution to journalArticle

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AU - Abboud, P. M.

AU - Chapleau, M. W.

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