Blebbistatin protects iPSC-CMs from hypercontraction and facilitates automated patch-clamp based electrophysiological study

Li W, Luo X, Ulbricht Y, and Guan K.

Stem Cell Research, 2021.

Blebbistatin may enable scientists studying cardiac channelopathies to obtain high-quality data with higher throughput

Modeling cardiac channelopathies using the automated patch clamp (APC) method with induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has been challenging, in part due to difficulty maintaining the high quality of single iPSC-CMs during dissociation and recording. However, scientists report that using the myosin inhibitor blebbistatin throughout APC procedures improved cardiomyocyte preparation for electrophysiological studies, terminated cardiomyocyte contraction to prevent calcium paradox damage, improved INa and action potential recordings, and recapitulated phenotypes of Brugada syndrome.

To assess electrophysiological effects, scientists used Axion’s Maestro Edge platform to analyze the iPSC-CMs before and the application of three different concentrations of blebbistatin treatment. The findings demonstrated that blebbistatin 2.5 µM had no effects on electrical field potential of human iPSC-CMs but prevented their beating, and showed no differences in action potential duration, action potential amplitude, and resting membrane potential.