English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/71654
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:


EPAC signalling pathways are involved in low PO2 chemoreception in carotid body chemoreceptor cells

AuthorsRocher, Asunción CSIC ORCID; Cáceres, Ana Isabel; Almaraz, Laura; González, Constancio CSIC
Issue Date2009
CitationJournal of Physiology 587(16): 4015-4027 (2009)
AbstractChemoreceptor cells of the carotid bodies (CB) are activated by hypoxia and acidosis, responding with an increase in their rate of neurotransmitter release, which in turn increases the electrical activity in the carotid sinus nerve and evokes a homeostatic hyperventilation. Studies in isolated chemoreceptor cells have shown that moderate hypoxias (PO2 ≈ 46 mmHg) produces smaller depolarisations and comparable Ca2+ transients but a much higher catecholamine (CA) release response in intact CBs than intense acidic/hypercapnic stimuli (20% CO2, pH 6.6). Similarly, intense hypoxia (PO2 ≈ 20 mmHg) produces smaller depolarizations and Ca2+ transients in isolated chemoreceptor cells but a higher CA release response in intact CBs than a pure depolarizing stimulus (30-35 mM external K+). Studying the mechanisms responsible for these differences we have found the following. (1) Acidic hypercapnia inhibited ICa (∼60%; whole cell) and CA release (∼45%; intact CB) elicited by ionomycin and high K+. (2) Adenylate cyclase inhibition (SQ-22536; 80 μM) inhibited the hypoxic release response (>50%) and did not affect acidic/hypercapnic release, evidencing that the high gain of hypoxia to elicit neurotransmitter release is cAMP dependent. (3) The last effect was independent of PKA activation, as three kinase inhibitors (H-89, KT 5720 and Rp-cAMP; ≥ 10 × IC50) did not alter the hypoxic release response. (4) The Epac (exchange protein activated by cAMP) activator (8-pCPT-2′-O-Me-cAMP, 100 μM) reversed the effects of the cyclase inhibitor. (5) The Epac inhibitor brefeldin A (100 μM) inhibited (54%) hypoxic induced release. Our findings show for the first time that an Epac-mediated pathway mediates O2 sensing/transduction in chemoreceptor cells. © 2009 The Authors. Journal compilation © 2009 The Physiological Society.
Publisher version (URL)http://dx.doi.org/10.1113/jphysiol.2009.172072
Identifiersdoi: 10.1113/jphysiol.2009.172072
issn: 0022-3751
e-issn: 1469-7793
Appears in Collections:(IN) Artículos
(IBGM) Artículos
Files in This Item:
File Description SizeFormat 
EPAC signalling.pdf660,42 kBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.