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

PeerJ

article

Mingming Yang¹  Caroline Dart³  Tomoko Kamishima²  John M. Quayle² 

[1] Department of Cardiology, Zhongda Hospital, Medical School of Southeast University;Department of Cellular and Molecular Physiology, Institute of Translational Medicine;Department of Biochemistry, Institute of Integrative Biology

关键词: Metabolic inhibitor;    Hypoxia;    ATP;    Membrane potential;    Potassium channels;   

DOI  :  10.7717/peerj.10344

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

ATP-sensitive potassium (KATP) 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 KATP 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 DiBAC4(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.

【 授权许可】

CC BY