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Cyclic AMP and Epac Contribute to the Genesis of the Positive Interaction Between Hypoxia and Hypercapnia in the Carotid Body

  • Maria Ramirez
  • Laura Almaraz
  • Constancio Gonzalez
  • Asuncion RocherEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 758)

Abstract

Carotid body chemoreceptor cells in response to hypoxic and hypercapnic stimulus increase their resting rate of release of neurotransmitters and their action potential frequency in the carotid sinus sensory nerve. When chemoreceptor activity is assessed at the level of the carotid sinus nerve and on ventilation, there exists an interaction between hypoxic and hypercapnic stimulus so that the response to both stimuli combined is additive or more than additive, over a wide range of stimulation. It is not clear if this interaction occurs at chemoreceptor cell or directly acting on the sensory nerve. In the present work we demonstrate for the first time the existence of a positive interaction between hypoxic and hypercapnic-acidotic stimuli at the level of both, membrane potential depolarization and neurotransmitter release in rat and rabbit carotid body. Inhibition of adenylate cyclase (SQ-22536) abolished the positive interaction between stimuli and the Epac (exchange proteins activated by cAMP) activator 8-pCPT-2′-O-Me-cAMP reversed the effect of adenylate cyclase inhibition. These results suggest that this interaction between the two natural stimuli is mediated by cAMP via an Epac-dependent pathway, at least at the level of neurotransmitter release.

Keywords

cAMP Protein kinase A Epac Membrane potential Catecholamine release 

Notes

Acknowledgements

This work was supported by grants BFU2007-61848 (DGICYT), CIBER CB06/06/0050 (FISS-ICIII).

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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Maria Ramirez
    • 1
  • Laura Almaraz
    • 2
  • Constancio Gonzalez
    • 1
  • Asuncion Rocher
    • 1
    Email author
  1. 1.Departamento de Bioquímica y Biología Molecular y Fisiología. IBGM. Facultad de MedicinaCIBERES, Instituto de Salud Carlos III, Universidad de Valladolid-CSICValladolidSpain
  2. 2.Instituto de NeurocienciasUniversidad Miguel Hernández-CSICSan Juan de AlicanteSpain

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