Hypoxia and metabolic inhibitors alter the intracellular ATP:ADP ratio and membrane potential in human coronary artery smooth muscle cells.



Yang, Mingming, Dart, Caroline ORCID: 0000-0002-3509-8349, Kamishima, Tomoko and Quayle, John M ORCID: 0000-0003-2762-5011
(2020) Hypoxia and metabolic inhibitors alter the intracellular ATP:ADP ratio and membrane potential in human coronary artery smooth muscle cells. PeerJ, 8. e10344 - e10344.

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Abstract

ATP-sensitive potassium (K<sub>ATP</sub>) channels couple cellular metabolism to excitability, making them ideal candidate sensors for hypoxic vasodilation. However, it is still unknown whether cellular nucleotide levels are affected sufficiently to activate vascular K<sub>ATP</sub> channels during hypoxia. To address this fundamental issue, we measured changes in the intracellular ATP:ADP ratio using the biosensors Perceval/PercevalHR, and membrane potential using the fluorescent probe DiBAC<sub>4</sub>(3) in human coronary artery smooth muscle cells (HCASMCs). ATP:ADP ratio was significantly reduced by exposure to hypoxia. Application of metabolic inhibitors for oxidative phosphorylation also reduced ATP:ADP ratio. Hyperpolarization caused by inhibiting oxidative phosphorylation was blocked by either 10 µM glibenclamide or 60 mM K<sup>+</sup>. Hyperpolarization caused by hypoxia was abolished by 60 mM K<sup>+</sup> but not by individual K<sup>+</sup> channel inhibitors. Taken together, these results suggest hypoxia causes hyperpolarization in part by modulating K<sup>+</sup> channels in SMCs.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 27 Jan 2021 09:28
Last Modified: 27 Aug 2022 02:12
DOI: 10.7717/peerj.10344
URI: https://livrepository.liverpool.ac.uk/id/eprint/3114840