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Validation and Development of a Cell‐based Model of Acute Oxygen Sensing
Author(s) -
LIU MIN,
CHANG ANDY
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09429
Subject(s) - glomus cell , carotid body , depolarization , hypoxia (environmental) , microbiology and biotechnology , intracellular , biology , brainstem , cell type , receptor , oxygen , neurotransmitter , medicine , endocrinology , neuroscience , cell , chemistry , electrophysiology , biochemistry , organic chemistry
Located at the bifurcation of the carotid artery, the carotid body senses a decrease in blood oxygen to increase breathing within seconds. This chemosensory organ is important for physiological adaptation to low oxygen (hypoxia), and its activity is increased in chronic diseases like sleep‐disordered breathing, chronic heart failure, and metabolic syndrome. In the carotid body, neuroendocrine cells called glomus cells respond to hypoxia to stimulate afferent nerves that signal to brainstem respiratory centers. Several important steps of the response of glomus cells to hypoxia have been identified, including the inhibition of oxygen‐sensitive potassium currents, membrane depolarization, intracellular calcium increase, and neurotransmitter release. However, the exact oxygen sensor(s) and how it integrates with these downstream steps remains controversial. A major limitation in studying glomus cell sensory signaling is poor recovery of primary glomus cells from tissue, and a significant fraction of cultured glomus cells are not responsive to hypoxia. We are exploring whether the PC12 cell line, derived from a rat pheochromocytoma, can serve as a model for carotid body oxygen sensing. Previously, other labs demonstrated that PC12 cells have similar acute responses to hypoxia as glomus cells, and more recent gene expression studies show that PC12 cells express some key signaling components implicated in carotid body oxygen sensing. Here, we confirm that hypoxia inhibits potassium currents and causes membrane depolarization in PC12 cells and describe the subtypes of potassium channels found in PC12. We hope to develop the PC12 cell line as a more tractable cell‐based model of acute oxygen sensing and to study the interactions of putative oxygen sensors with downstream signaling through ion channels and neurotransmitter release using this model.