At present, cardiovascular disease has become the greatest threat to human health. In the field of biomedical research, the development of drugs that effectively improve the function of the heart and promote the improvement of symptoms of cardiovascular diseases has become a hot spot for researchers.
Researcher Yamazaki K et al. from Eisai , Japan , developed a novel method using the planar microelectrode array recording system ( MED64 ) to easily obtain a cluster of cells that meet the requirements, thereby establishing a degree to which the QT interval can be evaluated. System.
In the initial experiments, the researchers found that the myocardial cluster cells induced by human embryonic stem cells, QT interval and other field potential time course ( FPD ) response to hERG channel blockers, can have a great difference from no response to overreaction . Therefore, they treated cell clusters with a 100 nM concentration of Cisapride (a hERG channel blocker) and screened cells using a planar microelectrode array recording system ( MED64 ) to select 5-20% of the FPDc extension as a standard. Then, the target compound is incubated with the cell cluster obtained in accordance with the standard.
The cell cluster obtained by the above method is suitable for evaluating the effect of the compound on the ion channel, thereby affecting the QT interval. This is the earliest report, using MED64 to detect potential changes, screening for appropriate cell clusters, and establishing a method to evaluate the extent of QT interval.
The study by Yamazaki K et al. provides a more sophisticated system for drug screening using induced cells. It will become a reality to quickly and accurately obtain the effect of drugs on the cells of interest.
The planar microelectrode array recording system ( MED64 ) is currently the best assistant for ex vivo electrophysiological studies. MED64 has been successfully applied to:
•       Central nervous system: such as cerebral cortex, hippocampus, retina, suprachiasmatic nucleus, amygdala;
•       Peripheral nervous system: such as dorsal root ganglion
•       Myocardium (atrial, ventricular, cardiomyocytes) and other easily excitable tissues (such as smooth muscle)
•       Acute brain slices , sectioned explants and isolated cultures .
Source: http://
A novel method of selecting human embryonic stem cell-derived cardiomyocyte clusters for assessment of potential to influence QT interval.
Yamazaki K, Hihara T, Taniguchi T, Kohmura N, Yoshinaga T, Ito M, Sawada K.
SourceEisai Product Creation Systems, Eisai Co., Ltd.,
Abstract
Physiologically relevant assessment of delayed repolarization is necessary in drug development. In our preliminary experiments on the evaluation using a multielectrode recording system, we had found that the responsiveness of field potential duration (FPD), as QT-like intervals, to hERG channel blockers differed Much from non-responders to excessive responders in human embryonic stem cell-derived cardiomyocyte clusters. Thus, we report a novel method of selecting clusters suitable for evaluating compounds for the assessment. Clusters were treated with cisapride, a hERG channel blocker, at 100nM, And selected with criteria of 5-20% of corrected FPD (FPDc) prolongation. Then, selected clusters were treated with reference compounds. FPDc was prolonged by blockade of the hERG channel (E-4031 and dl-sotalol) and KvLQT1 channel (chromanol 293B and HMR1556), and by activation of the sodium channel (veratridine) and calcium channel (Bay K8644). FPDc was shortened by calcium channel blockage (verapamil, nifedipine and diltiazem) and by K(ATP) channel activation (pinacidil).
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