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Article
Inhibition of Adenylate Cyclase Attenuates Muscarinic Ca2+ Signaling by a PKA-Independent Mechanism in Rat Carotid Body Type I Cells
Respiratory Physiology & Neurobiology
  • Carrie M. Thompson
  • Christopher N. Wyatt, Wright State University - Main Campus
Document Type
Article
Publication Date
1-31-2011
Abstract
Carotid body (CB) Type I cells respond to hypoxia by releasing excitatory and inhibitory neurotransmitters. This mechanism leads to increased firing of the carotid sinus nerve (CSN) which alters breathing to maintain blood gases within the physiological range. Acetylcholine targets both muscarinic and nicotinic receptors in the rat CB, acting postsynaptically on CSN and presynaptically on Type I cells. Muscarinic Ca2+ signaling is inhibited by the activation of Gi-coupled receptors including histamine H3 receptors. Here inhibition of adenylate cyclase with SQ22536 mimicked H3 receptor activation. Using Ca2+ imaging techniques it was observed that inhibition of muscarinic Ca2+ signaling was independent of protein kinase A (PKA) as PKA inhibitors H89 and KT5720 were without effect on the muscarinic Ca2+ response. By contrast the Epac (exchange protein activated by cAMP) inhibitor brefeldin A inhibited muscarinic Ca2+ signaling whereas the Epac activator 8-pCPT-2′-O-Me-cAMP-AM potentiated Ca2+ signaling. Thus in Type I cells inhibition of adenylate cyclase inhibited muscarinic Ca2+ signaling via a PKA-independent pathway that may rely upon modulation of Epac.
DOI
10.1016/j.resp.2010.09.013
Citation Information
Carrie M. Thompson and Christopher N. Wyatt. "Inhibition of Adenylate Cyclase Attenuates Muscarinic Ca2+ Signaling by a PKA-Independent Mechanism in Rat Carotid Body Type I Cells" Respiratory Physiology & Neurobiology Vol. 175 Iss. 1 (2011) p. 90 - 96 ISSN: 1569-9048
Available at: http://works.bepress.com/christopher_wyatt/28/