Montalbano Alberto, Sala Cesare, Altadonna Ginevra Chioccioli, Becchetti Andrea, Arcangeli Annarosa
Department of Experimental and Clinical Medicine, University of Florence, I-50134, Florence, Italy.
Department of Medical Biotechnologies, University of Siena, Strada delle Scotte, 53100, Siena, Italy.
Heliyon. 2023 Sep 19;9(10):e20112. doi: 10.1016/j.heliyon.2023.e20112. eCollection 2023 Oct.
Pharmacological studies aimed at the development of newly synthesized drugs directed against ion channels (as well as genetic studies of ion channel mutations) involve the development and use of transfected cells. However, the identification of the best clone, in terms of transfection efficiency, is often a time consuming procedure when performed through traditional methods such as manual patch-clamp. On the other hand, the use of other faster techniques, such as for example the IF, are not informative on the effective biological functionality of the transfected ion channel(s). In the present work, we used the high throughput automated ion channel reader (ICR) technology (ICR8000 Aurora Biomed Inc.) that combine atomic absorption spectroscopy with a patented microsampling process to accurately measure ion flux in cell-based screening assays. This technology indeed helped us to evaluate the transfection efficiency of hERG1 and hKv1.3 channels respectively on the HEK-293 and CHO cellular models. Moreover, as proof of the validity of this innovative method, we have corroborated these data with the functional characterization of the potassium currents carried out by the same clones through patch-clamp recordings. The results obtained in our study are promising and represent a valid methodological strategy to screen a large number of clones simultaneously and to pharmacologically evaluate their functionality within an extremely faster timeframe.
旨在开发针对离子通道的新合成药物的药理学研究(以及离子通道突变的遗传学研究)涉及转染细胞的开发和使用。然而,通过传统方法(如手动膜片钳)来鉴定转染效率方面的最佳克隆,往往是一个耗时的过程。另一方面,使用其他更快的技术,例如免疫荧光法(IF),对于转染的离子通道的有效生物学功能并无信息价值。在本研究中,我们使用了高通量自动离子通道读取器(ICR)技术(ICR8000,奥罗拉生物医学公司),该技术将原子吸收光谱与专利微采样过程相结合,以在基于细胞的筛选试验中准确测量离子通量。这项技术确实帮助我们分别在HEK - 293和CHO细胞模型上评估了hERG1和hKv1.3通道的转染效率。此外,作为这种创新方法有效性的证明,我们通过膜片钳记录对相同克隆所携带的钾电流进行功能表征,从而证实了这些数据。我们研究中获得的结果很有前景,代表了一种有效的方法策略,可同时筛选大量克隆,并在极短的时间内从药理学角度评估它们的功能。