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The Journal of Neuroscience, December 19, 2007, 27(51):14049-14058; doi:10.1523/JNEUROSCI.4254-07.2007

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Behavioral/Systems/Cognitive
TASK Channels Determine pH Sensitivity in Select Respiratory Neurons But Do Not Contribute to Central Respiratory Chemosensitivity

Daniel K. Mulkey, ^* Edmund M. Talley, ^* Ruth L. Stornetta, Audra R. Siegel, Gavin H. West, Xiangdong Chen, Neil Sen, Akshitkumar M. Mistry, Patrice G. Guyenet, and Douglas A. Bayliss

Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908

Correspondence should be addressed to Douglas A. Bayliss, Department of Pharmacology, University of Virginia, Charlottesville, VA 22908-0735. Email: dab3y{at}virginia.edu

Central respiratory chemoreception is the mechanism by which the CNS maintains physiologically appropriate pH and PCO₂ via control of breathing. A prominent hypothesis holds that neural substrates for this process are distributed widely in the respiratory network, especially because many neurons that make up this network are chemosensitive in vitro. We and others have proposed that TASK channels (TASK-1, K_2P3.1 and/or TASK-3, K_2P9.1) may serve as molecular sensors for central chemoreception because they are highly expressed in multiple neuronal populations in the respiratory pathway and contribute to their pH sensitivity in vitro. To test this hypothesis, we examined the chemosensitivity of two prime candidate chemoreceptor neurons in vitro and tested ventilatory responses to CO₂ using TASK channel knock-out mice. The pH sensitivity of serotonergic raphe neurons was abolished in TASK channel knock-outs. In contrast, pH sensitivity of neurons in the mouse retrotrapezoid nucleus (RTN) was fully maintained in a TASK null background, and pharmacological evidence indicated that a K⁺ channel with properties distinct from TASK channels contributes to the pH sensitivity of rat RTN neurons. Furthermore, the ventilatory response to CO₂ was completely retained in single or double TASK knock-out mice. These data rule out a strict requirement for TASK channels or raphe neurons in central respiratory chemosensation. Furthermore, they indicate that a non-TASK K⁺ current contributes to chemosensitivity of RTN neurons, which are profoundly pH-sensitive and capable of driving respiratory output in response to local pH changes in vivo.

Key words: background potassium channel; KCNK; raphe; RTN; pH signaling; brain slice; plethysmography

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Received Sept. 17, 2007; revised Nov. 8, 2007; accepted Nov. 8, 2007.

Correspondence should be addressed to Douglas A. Bayliss, Department of Pharmacology, University of Virginia, Charlottesville, VA 22908-0735. Email: dab3y{at}virginia.edu

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