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.
Text
Hypoxia and metabolic inhibitors alter the intracellular ATPADP ratio and membrane potential in human coronary artery smooth.pdf - Published version Download (1MB) | Preview |
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 |
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Uncontrolled Keywords: | Metabolic inhibitor, Hypoxia, ATP, Membrane potential, Potassium channels |
Depositing User: | Symplectic Admin |
Date Deposited: | 27 Jan 2021 09:28 |
Last Modified: | 18 Jan 2023 23:02 |
DOI: | 10.7717/peerj.10344 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3114840 |