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The Thirty-Fifth Anniversary of K+ Channels in O2 Sensing: What We Know and What We Don’t Know.
Version 1
: Received: 6 December 2023 / Approved: 7 December 2023 / Online: 7 December 2023 (07:11:34 CET)
A peer-reviewed article of this Preprint also exists.
Rocher, A.; Aaronson, P.I. The Thirty-Fifth Anniversary of K+ Channels in O2 Sensing: What We Know and What We Don’t Know. Oxygen 2024, 4, 53-89. Rocher, A.; Aaronson, P.I. The Thirty-Fifth Anniversary of K+ Channels in O2 Sensing: What We Know and What We Don’t Know. Oxygen 2024, 4, 53-89.
Abstract
On the thirty-fifth anniversary of the first description of O2-sensitive K+ channels in the carotid body chemoreceptors [1], O2 sensing remains a salient issue in the literature. Whereas much has been learned about this subject, important questions such as the identity of the specific K+ channel subtype(s) responsible for O2 sensing by chemoreceptors and the mechanism(s) by which their activities are altered by hypoxia have not yet been definitively answered. O2 sensing is a fundamental biological process necessary for the acute and chronic responses to varying environmental O2 levels which allow organisms to adapt to hypoxia. Whereas chronic responses depend on the modulation of hypoxia-inducible transcription factors which determine the expression of numerous genes encoding enzymes, transporters and growth factors, acute responses rely mainly on the dynamic modulation of ion channels by hypoxia, causing adaptive changes in cell excitability, contractility, and secretory activity in specialized tissues. The most widely studied oxygen-sensitive ion channels are potassium channels but oxygen sensing by members of both the calcium and sodium channel families has also been demonstrated. Given the explosion of information on this topic, in this review we will focus on the mechanisms of physiological oxygen chemotransduction by PO2-dependent K+ channels, with particular emphasis on their function in carotid body chemoreceptor cells (CBCC) and pulmonary artery smooth muscle cells (PASMC), highlighting areas of consensus and controversy within the field. We will first describe the most well-established concepts, those reproduced in multiple laboratories, and then discuss selected observations or questions that remain unresolved, and that limit our progress in this field.
Keywords
O2 sensing; carotid body; hypoxia; hypoxic pulmonary vasoconstriction; BKCa channel; KV channel; TASK channel; mitochondria; reactive oxygen species; redox
Subject
Biology and Life Sciences, Anatomy and Physiology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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