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Cardiovascular Research Institute

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Light-Activated Dynamic Clamp Using iPSC-Derived Cardiomyocytes.

TitleLight-Activated Dynamic Clamp Using iPSC-Derived Cardiomyocytes.
Publication TypeJournal Article
Year of Publication2018
AuthorsQuach, B, Krogh-Madsen, T, Entcheva, E, Christini, DJ
JournalBiophys J
Date Published2018 Dec 04

iPSC-derived cardiomyocytes (iPSC-CMs) are a potentially advantageous platform for drug screening because they provide a renewable source of human cardiomyocytes. One obstacle to their implementation is their immature electrophysiology, which reduces relevance to adult arrhythmogenesis. To address this, dynamic clamp is used to inject current representing the insufficient potassium current, I, thereby producing more adult-like electrophysiology. However, dynamic clamp requires patch clamp and is therefore low throughput and ill-suited for large-scale drug screening. Here, we use optogenetics to generate such a dynamic-clamp current. The optical dynamic clamp (ODC) uses outward-current-generating opsin, ArchT, to mimic I, resulting in more adult-like action potential morphology, similar to I injection via classic dynamic clamp. Furthermore, in the presence of an I blocker, ODC revealed expected action potential prolongation and reduced spontaneous excitation. The ODC presented here still requires an electrode to measure V but provides a first step toward contactless dynamic clamp, which will not only enable high-throughput screening but may also allow control within multicellular iPSC-CM formats to better recapitulate adult in vivo physiology.

Alternate JournalBiophys. J.
PubMed ID30447994
PubMed Central IDPMC6289097
Grant ListF31 HL134209 / HL / NHLBI NIH HHS / United States
R01 EB016407 / EB / NIBIB NIH HHS / United States
R01 HL111649 / HL / NHLBI NIH HHS / United States
U01 HL136297 / HL / NHLBI NIH HHS / United States