Ouyang, M.; Zhou, B.; Li, C.; Deng, L. Characterization of PDGF-Induced Subcellular Calcium Regulation through Calcium Channels in Airway Smooth Muscle Cells by FRET Biosensors. Biosensors2024, 14, 179.
Ouyang, M.; Zhou, B.; Li, C.; Deng, L. Characterization of PDGF-Induced Subcellular Calcium Regulation through Calcium Channels in Airway Smooth Muscle Cells by FRET Biosensors. Biosensors 2024, 14, 179.
Ouyang, M.; Zhou, B.; Li, C.; Deng, L. Characterization of PDGF-Induced Subcellular Calcium Regulation through Calcium Channels in Airway Smooth Muscle Cells by FRET Biosensors. Biosensors2024, 14, 179.
Ouyang, M.; Zhou, B.; Li, C.; Deng, L. Characterization of PDGF-Induced Subcellular Calcium Regulation through Calcium Channels in Airway Smooth Muscle Cells by FRET Biosensors. Biosensors 2024, 14, 179.
Abstract
The homeostasis of cellular calcium is fundamental for many physiological activities, while calcium levels maintain inhomogeneous within cells. During the onset of asthma, epithelial and inflammatory cells secrete platelet derived growth factor (PDGF), inducing proliferation and migration of airway smooth muscle (ASM) to the epidermal layer, narrowing the airway. The regulation of ASM cells by PDGF is closely related to the conduction of calcium signals. In this work, we generated subcellular-targeted FRET biosensors to investigate calcium regulations at different compartments of ASM cells. PDGF-induced cytoplasmic calcium [Ca2+]C increase was attributed from both extracellular calcium influx and endoplasmic reticulum (ER) calcium [Ca2+]ER release, which was partially regulated by PLC-IP3R pathway. Interestingly, removal of extracellular calcium influx led to inhibited ER calcium release, likely through inhibitory effect on calcium-dependent activation of ER ryanodine receptor. Inhibition of L-type calcium channel on plasma membrane, or SERCA pump on ER resulted in both reduced [Ca2+]C and [Ca2+]ER from PDGF stimulation, while IP3R channel inhibition led to reduced [Ca2+]C only. Inhibited SERCA pump caused immediate [Ca2+]C increase and [Ca2+]ER decrease, indicating an active calcium exchange between cytosol and ER storage in resting cells. PDGF-induced calcium at outer mitochondrial membrane sub-region showed similar regulatory response to cytosolic calcium, not influenced by inhibition of mitochondrial calcium uniporter channel. Therefore, our work identified calcium flow pathways among extracellular medium, cell cytosol, and ER by regulatory calcium channels. Particularly, extracellular calcium flow has an essential function to fully activate ER calcium release.
Biology and Life Sciences, Biochemistry and Molecular Biology
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