2025 CONVENTION
Excipient-channel interaction: Polysorbate 80 inhibits Kv4.3 A-type potassium currents
Polysorbate 80 (PS80) is a non-ionic detergent that is commonly used as an emulsifying agent in pharmaceuticals, food production, and cosmetics. Building on our prior finding that PS80 suppresses Nav1.7 and Nav1.5 in state- and use-dependent manners, we investigated its effects on Kv4.3 (KCND3), a principal mediator of fast A-type K⁺ current that shapes neuronal firing and early cardiac repolarization. Whole-cell patch-clamp recordings from Kv4.3-expressing CHO cells showed that PS80 decreases peak current in a concentration-dependent manner and more strongly reduces the current integral during depolarization. The decay phase was best fit by a bi-exponential model, and PS80 accelerated both tau_fast and tau_slow of inactivation. During depolarizing pulse trains, fractional block developed mono-exponentially within each step and accumulated with use, consistent with an apparent open-channel interaction and time-dependent block. These data extend PS80\'s modulatory spectrum from sodium to potassium channels and raise formulation-relevant concerns for excitable tissues. Collectively, the data indicate that routine excipients can display quantifiable ion-channel activity, meriting consideration in study design, analysis, and risk assessment.