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Connexin 26 is responsible for ATP release underlying central CO2 chemosensitivity
Author(s) -
Huckstepp Robert Timothy Richard,
Eason Robert C,
Bihi Rachid id,
Dicke Nikolai,
Willecke Klaus,
Spyer K. Michael,
Gourine Alexander V,
Dale Nicholas
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1026.2
Subject(s) - connexin , gap junction , in vivo , microbiology and biotechnology , chemistry , biology , medulla oblongata , biophysics , central nervous system , neuroscience , intracellular
Although chemosensitive areas of the medulla oblongata have been defined, the cell types and mechanisms involved in CO 2 chemosensory transduction there remain unknown. Recently, a causal link between ATP release from the surface of the ventro‐lateral medulla (VLM) and the hypercapnic ventilatory response (HVR) in vivo has been established. By employing horizontal slices of the VLM, we studied CO 2 ‐triggered ATP release in vitro , which was greatly reduced by pharmacological inhibition of connexin hemichannels. The dorso‐ventral distribution of connexin 26 (C×26) ascertained via real time PCR, immunofluorescence and a lacZ knock‐in reporter, combined with the CO 2 ‐senistivity of C×26 transfected HeLa cells makes it the most likely candidate. Furthermore we have documented direct gating of C×26 in response to changes of PCO 2 in excised membrane patches. CO 2 ‐ dependent dye loading of tissue slices with carboxyfluorescein stained cells in the pia mater, sub‐pial astrocytes and cells associated with penetrating blood vessels. Application of gap‐junction antagonists greatly reduced ATP release in response to elevated CO 2 and the HVR in vivo . Therefore we propose that ATP is released from sub‐pial astrocytes and pial cells through C×26 hemichannels in response to alterations in PCO 2 , with C×26 acting as the chemosensory transducer and the conduit for ATP release. Research was supported by the BBSRC and MRC