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A role for TASK-1 (KCNK3) channels in the chemosensory control of breathing

Trapp, S.; Isabel Aller, M.; Wisden, W.; Gourine, A. V.; (2008) A role for TASK-1 (KCNK3) channels in the chemosensory control of breathing. Journal of Neuroscience , 28 (35) pp. 8844-8850. 10.1523/JNEUROSCI.1810-08.2008. Green open access

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Abstract

Acid-sensitive K+ channels of the tandem P-domain K+-channel family (TASK-1 and TASK-3) have been implicated in peripheral and central respiratory chemosensitivity; however, because of the lack of decisive pharmacological agents, the final proof of the role of the TASK channel in the chemosensory control of breathing has been missing. In the mouse, TASK-1 and TASK-3 channels are dispensable for central respiratory chemosensitivity (Mulkey et al., 2007Go). Here, we have used knock-out animals to determine whether TASK-1 and TASK-3 channels play a role in the carotid body function and chemosensory control of breathing exerted by the carotid body chemoreceptors. Ventilatory responses to hypoxia (10% O2 in inspired air) and moderate normoxic hypercapnia (3–6% CO2 in inspired air) were significantly reduced in TASK-1 knock-out mice. In contrast, TASK-3-deficient mice showed responses to both stimuli that were similar to those developed by their wild-type counterparts. TASK-1 channel deficiency resulted in a marked reduction of the hypoxia (by 49%)- and CO2 (by 68%)-evoked increases in the carotid sinus nerve chemoafferent discharge recorded in the in vitro superfused carotid body/carotid sinus nerve preparations. Deficiency in both TASK-1 and TASK-3 channels increased baseline chemoafferent activity but did not cause a further reduction of the carotid body chemosensory responses. These observations provide direct evidence that TASK-1 channels contribute significantly to the increases in the carotid body chemoafferent discharge in response to a decrease in arterial PO2 or an increase in PCO2/[H+]. TASK-1 channels therefore play a key role in the control of ventilation by peripheral chemoreceptors.

Type: Article
Title: A role for TASK-1 (KCNK3) channels in the chemosensory control of breathing
Open access status: An open access version is available from UCL Discovery
DOI: 10.1523/JNEUROSCI.1810-08.2008
Publisher version: http://dx.doi.org/10.1523/JNEUROSCI.1810-08.2008
Language: English
Additional information: Published by the Society of Neuroscience. Article reproduced here for non-commercial purposes under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license. For further information see: http://creativecommons.org/licenses/by-nc-sa/3.0/
Keywords: Carotid body, chemosensitivity, hypercapnia, hypoxia, respiration, TASK
UCL classification: UCL > Provost and Vice Provost Offices > VP: Education > UCL Arena Centre
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/20118
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