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A near-infrared fluorescent voltage-sensitive dye allows for moderate-throughput analyses of human induced pluripotent stem cell-derived cardiomyocytes American Journal of Physiology - Heart and Circulatory Physiology




Human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM)-based assays are emerging as a promising tool for the in vitro pre-clinical screening of QT interval-prolonging side effects of drugs in development. A major impediment to the widespread use of human iPSC-CM assays is the low throughput of the currently available electrophysiological tools. To test the precision and applicability of the near-infrared fluorescent voltage-sensitive dye di-4-ANBDQBS for moderate-throughput electrophysiological analyses, we compared simultaneous transmembrane voltage (Vm) and optical action potential (AP) recordings in human iPSC-CM loaded with di-4-ANBDQBS. Optical AP recordings tracked Vm with high precision, generating nearly identical values for action potential duration (APD10, APD50 and APD90). Human iPSC-CM tolerated repeated laser exposure, with stable optical AP parameters recorded over a 30 min study period. Optical AP recordings appropriately tracked changes in repolarization induced by pharmacological manipulation. Finally, di-4-ANBDQBS allowed for moderate-throughput analyses, increasing throughput >10-fold over traditional patch clamp technique. We conclude that the voltage-sensitive dye di-4-ANBDQBS allows for high precision optical AP measurements that markedly increase the throughput for electrophysiological characterization of human iPSC-CMs.

Author List

Angelica Lopez-Izquierdo, Mark Warren, Michael Reidel, Scott Cho, Shuping Lai, Robert Lux, Kenneth Spitzer, Ivor Benjamin, Martin Tristani-Firouzi, and Chuanchau Jou


Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin

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