QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 27, 2008, 28(35):8844-8850; doi:10.1523/JNEUROSCI.1810-08.2008

This Article Free Access Article Free Access Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Trapp, S. Articles by Gourine, A. V. Search for Related Content PubMed PubMed Citation Articles by Trapp, S. Articles by Gourine, A. V.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
A Role for TASK-1 (KCNK3) Channels in the Chemosensory Control of Breathing

Stefan Trapp,^1,2 M. Isabel Aller,³ William Wisden,⁴ and Alexander V. Gourine⁵

¹Department of Anaesthetics, Pain Medicine and Intensive Care, Chelsea and Westminster Hospital, Imperial College London, London SW10 9NH, United Kingdom, ²Biophysics Section, Blackett Laboratory, Imperial College London, London SW7 2AZ, United Kingdom, ³Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández de Elche, Campus de San Juan, Apartado 18, Sant Joan d'Alacant, Spain, ⁴Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom, and ⁵Department of Physiology, University College London, London WC1E 6BT, United Kingdom

Correspondence should be addressed to Alexander V. Gourine, Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK. Email: a.gourine{at}ucl.ac.uk

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., 2007). 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 P_O2 or an increase in P_CO2/[H⁺]. TASK-1 channels therefore play a key role in the control of ventilation by peripheral chemoreceptors.

Key words: carotid body; chemosensitivity; hypercapnia; hypoxia; respiration; TASK

---

Received Dec. 24, 2007; revised July 16, 2008; accepted July 29, 2008.

Correspondence should be addressed to Alexander V. Gourine, Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK. Email: a.gourine{at}ucl.ac.uk

This article has been cited by other articles:

				K. M. Spyer and A. V. Gourine Chemosensory pathways in the brainstem controlling cardiorespiratory activity Phil Trans R Soc B, September 12, 2009; 364(1529): 2603 - 2610. [Abstract] [Full Text] [PDF]

				C. N. Wyatt and C. Peers Hetero or homo, hypoxia has them all J. Physiol., June 15, 2009; 587(12): 2717 - 2718. [Full Text] [PDF]

				D. Kim, E. J. Cavanaugh, I. Kim, and J. L. Carroll Heteromeric TASK-1/TASK-3 is the major oxygen-sensitive background K+ channel in rat carotid body glomus cells J. Physiol., June 15, 2009; 587(12): 2963 - 2975. [Abstract] [Full Text] [PDF]

				K. M. Spyer To breathe or not to breathe? That is the question Exp Physiol, January 1, 2009; 94(1): 1 - 10. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help