A HCO3--dependent mechanism involving soluble adenylyl cyclase for the activation of Ca2+ currents in locus coeruleus neurons

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Article

Imber, Ann N.¹  Santin, Joseph M.²  Graham, Cathy D.¹  Putnam, Robert W.¹ 

[1] Wright State Univ, Boonshoft Sch Med, Dept Neurosci Cell Biol & Physiol, Dayton, OH 45435 USA

[2] Wright State Univ, Dept Biol Sci, Dayton, OH 45435 USA

关键词: Central control of breathing;    L-type Ca2+ channel;    Panic disorder;    KH7;    Development;    Transmembrane adenylyl cyclase;   

DOI  :  10.1016/j.bbadis.2014.07.027

来源: Elsevier

【 摘 要 】

Hypercapnic acidosis activates Ca2+ channels and increases intracellular Ca2+ levels in neurons of the locus coeruleus, a known chemosensitive region involved in respiratory control. We have also shown that large conductance Ca2+-activated K+ channels, in conjunction with this pathway, limits the hypercapnic-induced increase in firing rate in locus coeruleus neurons. Here, we present evidence that the Ca2+ current is activated by a HCO3--sensitive pathway. The increase in HCO3- associated with hypercapnia activates HCO3--sensitive adenylyl cyclase (soluble adenylyl cyclase). This results in an increase in cyclic adenosine monophosphate levels and activation of Ca2+ channels via cyclic adenosine monophosphate-activated protein kinase A. We also show the presence of soluble adenylyl cyclase in the cytoplasm of locus coeruleus neurons, and that the cyclic adenosine monophosphate analogue db-cyclic adenosine monophosphate increases Ca-i(2+). Disrupting this pathway by decreasing HCO3- levels during acidification or inhibiting either soluble adenylyl cyclase or protein kinase A, but not transmembrane adenylyl cyclase, can increase the magnitude of the firing rate response to hypercapnia in locus coeruleus neurons from older neonates to the same extent as inhibition of K+ channels. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

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