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AMPK facilitates the hypoxic ventilatory response through non-adrenergic mechanisms at the brainstem.
- Source :
-
Pflügers Archiv: European Journal of Physiology . Jan2023, Vol. 475 Issue 1, p89-99. 11p. - Publication Year :
- 2023
-
Abstract
- We recently demonstrated that the hypoxic ventilatory response (HVR) is facilitated by the AMP-activated protein kinase (AMPK) in catecholaminergic neural networks that likely lie downstream of the carotid bodies within the caudal brainstem. Here, we further subcategorise the neurons involved, by cross-comparison of mice in which the genes encoding the AMPK-α1 (Prkaa1) and AMPK-α2 (Prkaa2) catalytic subunits were deleted in catecholaminergic (TH-Cre) or adrenergic (PNMT-Cre) neurons. As expected, the HVR was markedly attenuated in mice with AMPK-α1/α2 deletion in catecholaminergic neurons, but surprisingly was modestly augmented in mice with AMPK-α1/α2 deletion in adrenergic neurons when compared against a variety of controls (TH-Cre, PNMT-Cre, AMPK-α1/α2 floxed). Moreover, AMPK-α1/α2 deletion in catecholaminergic neurons precipitated marked hypoventilation and apnoea during poikilocapnic hypoxia, relative to controls, while mice with AMPK-α1/α2 deletion in adrenergic neurons entered relative hyperventilation with reduced apnoea frequency and duration. We conclude, therefore, that AMPK-dependent modulation of non-adrenergic networks may facilitate increases in ventilatory drive that shape the classical HVR, whereas AMPK-dependent modulation of adrenergic networks may provide some form of negative feedback or inhibitory input to moderate HVR, which could, for example, protect against hyperventilation-induced hypocapnia and respiratory alkalosis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00316768
- Volume :
- 475
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Pflügers Archiv: European Journal of Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 161159280
- Full Text :
- https://doi.org/10.1007/s00424-022-02713-8