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A functional and robust cellular model for high-throughput screening of piezo1 modulators
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A functional and robust cellular model for high-throughput screening of piezo1 modulators
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Journal Article
A functional and robust cellular model for high-throughput screening of piezo1 modulators
2026
Overview
The Piezo1 channel, a mechanosensitive non-selective cation channel, plays a critical role in mediating calcium (Ca
2+
) influx in response to mechanical stimuli, which is vital for numerous physiological functions. However, the specificity and potency of current Piezo1 modulators are limited, and the existing screening methodologies are not sufficiently designed for high-throughput screening (HTS). To address these challenges, we developed a customized cellular model aimed at enhancing HTS efficiency for identifying potent and selective Piezo1 modulators. We utilized a cellular model that incorporates anoctamin-1 (ANO1), a calcium-activated chloride channel, along with a green fluorescent protein mutant with ultra-high halide sensitivity (YFP-H148Q/I152L) to monitor intracellular ion concentrations through fluorescence. This model can accurately detect changes in intracellular iodine ion (I
⁻
) concentration and rapidly and sensitively screen drugs targeting the Piezo1 channel, demonstrating exceptional performance in high-throughput screening (HTS). Our development of a pharmacological cell screening model specifically designed for Piezo1 provides a valuable tool for investigating Piezo1 modulators and their pathophysiological roles in vitro.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
