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The pH-Sensitive Potassium Channel TASK-1 Is a Chemosensor for Central Respiratory Regulation in Rats

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Abstract

TWIK-related acid-sensitive potassium channel-1 (TASK-1) is a “leak” potassium channel sensitive to extracellular protons. It contributes to setting the resting potential in mammalian neurons. TASK-1 channels are widely expressed in respiratory-related neurons in the central nervous system. Inhibition of TASK-1 by extracellular acidosis can depolarize and increase the excitability of these cells. Here we describe the distribution of TASK-1 in the rat brainstem and show that TASK-1 mRNAs are present in respiratory-related nuclei in the ventrolateral medulla, which have been proposed as neural substrates for central chemoreception in rats. After inhalation of 8% CO2 for 30 and 60 min, TASK-1 mRNA levels in positive-expression neurons were remarkably upregulated. Injection of the TASK-1 blocker anandamide (AEA) into the rat lateral cerebral ventricle, showed a significant excitement of respiratory at 10 min posttreatment, with a marked decrease in inspiratory and expiratory durations and an increased frequency of respiration. We suggest that TASK-1 channel may serve as a chemosensor for in central respiration and may contribute to pH-sensitive respiratory effects. TASK-1 channel might be an attractive candidate for sensing H+/CO2 in several respiratory-related nuclei in the brainstem. It is likely that TASK-1 participates in pH-sensitive chemical regulation in the respiratory center under physiological and pathological conditions.

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Funding

This study was supported by grants from the Natural Science Foundation of China (nos. 31560269, 31601030, and 30960173) and the Foundation for High-level Talents of Shihezi University (no. RCZX201448).

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Authors and Affiliations

  1. Department of Basic Medical Sciences, School of Medical, Shihezi University, 832000, Shihezi, China

    Q. Q. Li, K. X. Wan, C. T. Wang, F. X. Mao, J. L. Zhu, Z. M. Pan & R. Gao

  2. State Key Laboratory of Sheep Genetic Improvement and Healthy Production, **njiang Academy of Agricultural and Reclamation Sciences, 832000, Shihezi, China

    M. S. Xu, L. M. Wang & Y. Y. Zhang

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  1. Q. Q. Li
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  2. K. X. Wan
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Correspondence to R. Gao.

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Conflict of interest. The authors declare that they have no conflicts of interest.

Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

AUTHOR CONTRIBUTIONS

QL, KW, and MX contributed equally to this work.

RG and QL designed the study; JZ and ZP performed the experiments; LW, YZ, CW and FM analyzed the data; KW and MX wrote the manuscript.

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Li, Q.Q., Wan, K.X., Xu, M.S. et al. The pH-Sensitive Potassium Channel TASK-1 Is a Chemosensor for Central Respiratory Regulation in Rats. Mol Biol 54, 402–411 (2020). https://doi.org/10.1134/S0026893320030103

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