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

ATP-sensitive potassium (K _ATP ) 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 _ATP 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 ₄ (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 ⁺ . Hyperpolarization caused by hypoxia was abolished by 60 mM K ⁺ but not by individual K ⁺ channel inhibitors. Taken together, these results suggest hypoxia causes hyperpolarization in part by modulating K ⁺ channels in SMCs.
Competing Interests: The authors declare there are no competing interests.
(©2020 Yang et al.)