A novel near-infrared fluorescent probe for picrotoxin-site imaging of GABAA receptors on cell membranes.

In this study, a novel near-infrared fluorescent probe specifically recognizing the picrotoxin-binding site of the GABAA receptor (GABAAR) was synthesized via a one-step method, employing a coumarin derivative as the fluorophore and barbituric acid as the targeting unit. Spectral experiments demonstrated that the probe exhibits good photostability, pH stability, and polarity sensitivity, with significantly enhanced fluorescence in low-polarity environments. Cellular imaging results showed that the probe rapidly targets the cell membrane and achieves stable staining through picrotoxin-sensitive binding to GABAAR. The binding mode of the probe to the receptor was validated through picrotoxin competition experiments and molecular docking. This probe provides a new candidate scaffold for the design of cell membrane-targeting fluorescent probes and offers a potential tool for visualizing GABAAR binding sites.