人胚胎干細(xì)胞誘導(dǎo)產(chǎn)生之心肌細(xì)胞集群的新篩選方法，可用于評估QT間隔所受影響程度

    通過上述方法獲得的細(xì)胞集群，適用于評價化合物作用于離子通道，從而影響QT間隔的研究。這是目前最早報(bào)道的，利用MED64檢測電位改變，篩選獲得合適細(xì)胞集群，從而建立一個能夠評價QT間隔所受影響程度的方法。

      Yamazaki K等人的研究，為利用誘導(dǎo)產(chǎn)生的細(xì)胞進(jìn)行藥物篩選提供了一種更加完善的體系�？焖佟�準(zhǔn)確獲得藥物對目的細(xì)胞的作用效果，將成為現(xiàn)實(shí)。

平面微電極陣列記錄系統(tǒng)（MED64）是當(dāng)前進(jìn)行離體電生理研究的最佳助手，MED64已經(jīng)成功應(yīng)用于：

•       中樞神經(jīng)系統(tǒng)：如大腦皮層、海馬體、視網(wǎng)膜、視交叉上核、杏仁核；
•       周圍神經(jīng)系統(tǒng)：如背根神經(jīng)節(jié)
•       心肌 （心房、心室、心肌細(xì)胞）和其它易興奮組織（如平滑�。�
•       急性腦切片, 切片外植體和分離培養(yǎng)物.

文獻(xiàn)來源：

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., 5-1-3, Tokodai, Tsukuba, Ibaraki 300-2635, Japan.

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 greatly 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). Class Ia antiarrhythmic drugs, quinidine and disopyramide, prolonged FPDc. Selected clusters are appropriate for assessing the effects of compounds on ion channels affecting QT intervals. This is the first report of the establishment of an assessment system of potential to influence QT interval, using pharmacologically selected clusters.