Evaluating the proarrhythmic risk of delayed-action compounds in serum free cell culture conditions; serum-starvation accelerates/amplifies the effect of probucol on the KCNQ1 + KCNE1 channel.

In vitro testing procedures for evaluating acute effects of compound on ion channels, utilizing heterologous expression systems (HES), are well-established, while slowly manifesting delayed effects remain challenging to detect. For this, immortalized HES are exposed to the compounds for a longer time, in general 24 h. As these cells proliferate every 12-20 h, we evaluated if the proliferation status, and by extension cell metabolism, influences the delayed compound response. The intervention of halting cell proliferation by excluding serum from the culturing medium was evaluated on CHO cells, stably expressing the KCNQ1 + KCNE1 channel complex that mediates the slow delayed rectifier potassium current (I

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.