LKB1 is the gatekeeper of carotid body chemosensing and the hypoxic ventilatory response

MacMillan, S., Holmes, A. P., Dallas, M. L. ORCID: https://orcid.org/0000-0002-5190-0522, Mahmoud, A. D., Shipston, M. J., Peers, C., Hardie, D. G., Kumar, P. and Evans, A. M. (2022) LKB1 is the gatekeeper of carotid body chemosensing and the hypoxic ventilatory response. Communications Biology, 5. 642. ISSN 2399-3642 doi: 10.1038/s42003-022-03583-7

Abstract/Summary

The hypoxic ventilatory response (HVR) is critical to breathing and thus oxygen supply to the body and is primarily mediated by the carotid bodies. Here we reveal that carotid body afferent discharge during hypoxia and hypercapnia is determined by the expression of Liver Kinase B1 (LKB1), the principal kinase that activates the AMP-activated protein kinase (AMPK) during metabolic stresses. Conversely, conditional deletion in catecholaminergic cells of AMPK had no effect on carotid body responses to hypoxia or hypercapnia. By contrast, the HVR was attenuated by LKB1 and AMPK deletion. However, in LKB1 knockouts hypoxia evoked hypoventilation, apnoea and Cheyne-Stokes-like breathing, while only hypoventilation and apnoea were observed after AMPK deletion. We therefore identify LKB1 as an essential regulator of carotid body chemosensing and uncover a divergence in dependency on LKB1 and AMPK between the carotid body on one hand and the HVR on the other.

Additional Information	An Erratum to this article was published on 29/7/2022 and is available here https://doi.org/10.1038/s42003-022-03744-8
Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/106401
Identification Number/DOI	10.1038/s42003-022-03583-7
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Additional Information	An Erratum to this article was published on 29/7/2022 and is available here https://doi.org/10.1038/s42003-022-03744-8
Publisher	Nature Research
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