The epithelial sodium channel (ENaC) plays a central role in regulating sodium balance, blood pressure, and pulmonary fluid clearance. Despite its clinical relevance, progress in discovering new ENaC-targeting drugs has been limited by the lack of efficient, scalable functional assays.

In a recent study, researchers developed and validated an automated patch clamp (APC) approach using the SyncroPatch 384 platform to detect ENaC-mediated currents in a high-throughput format.

Using a HEK293 cell line stably expressing human αβγ-ENaC, the team demonstrated that the system reliably captures both inhibitory and stimulatory effects of known ENaC modulators, including the activator S3969 and the inhibitors γ-11 peptide and amiloride.

The study also addressed a key technical challenge: enzymatic cell detachment caused partial proteolytic activation of ENaC, reducing assay sensitivity. The authors established a recovery protocol that restores channel responsiveness to proteases like chymotrypsin, enabling better detection of activators that mimic physiological ENaC regulation.

Altogether, this work provides a robust and scalable method for screening ENaC modulators, supporting the development of new therapeutic strategies targeting ENaC-related diseases such as hypertension, cystic fibrosis, and pulmonary edema.

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Find the full article here: Automated patch-clamp recordings for detecting activators and inhibitors of the epithelial sodium channel (ENaC)

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