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Functional Properties of Mitochondria in the Type-1 Cell and Their Role in Oxygen Sensing

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Arterial Chemoreceptors in Physiology and Pathophysiology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 860))

Abstract

The identity of the oxygen sensor in arterial chemoreceptors has been the subject of much speculation. One of the oldest hypotheses is that oxygen is sensed through oxidative phosphorylation. There is a wealth of data demonstrating that arterial chemoreceptors are excited by inhibitors of oxidative phosphorylation. These compounds mimic the effects of hypoxia inhibiting TASK1/3 potassium channels causing membrane depolarisation calcium influx and neurosecretion. The TASK channels of Type-I cells are also sensitive to cytosolic MgATP. The existence of a metabolic signalling pathway in Type-1 cells is thus established; the contentious issue is whether this pathway is also used for acute oxygen sensing. The main criticism is that because cytochrome oxidase has a high affinity for oxygen (P50 ≈ 0.2 mmHg) mitochondrial metabolism should be insensitive to physiological hypoxia. This argument is however predicated on the assumption that chemoreceptor mitochondria are analogous to those of other tissues. We have however obtained new evidence to support the hypothesis that type-1 cell mitochondria are not like those of other cells in that they have an unusually low affinity for oxygen (Mills E, Jobsis FF, J Neurophysiol 35(4):405–428, 1972; Duchen MR, Biscoe TJ, J Physiol 450:13–31, 1992a). Our data confirm that mitochondrial membrane potential, NADH, electron transport and cytochrome oxidase activity in the Type-1 cell are all highly sensitive to hypoxia. These observations not only provide exceptionally strong support for the metabolic hypothesis but also reveal an unknown side of mitochondrial behaviour.

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Authors and Affiliations

  1. Department of Physiology Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK

    Keith J. Buckler & Philip J. Turner

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  1. Keith J. Buckler
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  2. Philip J. Turner
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Correspondence to Keith J. Buckler .

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Editors and Affiliations

  1. Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Faculty of Medicine and Health, Leeds, United Kingdom

    Chris Peers

  2. College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

    Prem Kumar

  3. Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, Ohio, USA

    Christopher Wyatt

  4. Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA

    Estelle Gauda

  5. Department of Biology, McMaster University, Hamilton, Ontario, Canada

    Colin A. Nurse

  6. Institute for Integrative Physiology and Center for Systems Biology of O(2) Sensing Biological Sciences Division, University of Chicago, Chicago, Illinois, USA

    Nanduri Prabhakar

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Buckler, K.J., Turner, P.J. (2015). Functional Properties of Mitochondria in the Type-1 Cell and Their Role in Oxygen Sensing. In: Peers, C., Kumar, P., Wyatt, C., Gauda, E., Nurse, C., Prabhakar, N. (eds) Arterial Chemoreceptors in Physiology and Pathophysiology. Advances in Experimental Medicine and Biology, vol 860. Springer, Cham. https://doi.org/10.1007/978-3-319-18440-1_9

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