Department of Biotechnology and Biosciences, University of Milano-Bicocca, P.za della Scienza 2, 20126, Milan, Italy.
Center for Nano Science and Technology, Istituto Italiano di Tecnologia, Milan, Italy.
J Transl Med. 2024 Nov 27;22(1):1068. doi: 10.1186/s12967-024-05902-4.
The use of light to control the activity of living cells is a promising approach in cardiac research due to its unparalleled spatio-temporal selectivity and minimal invasiveness. Ziapin2, a newly synthesized azobenzene compound, has recently been reported as an efficient tool for light-driven modulation of excitation-contraction coupling (ECC) in human-induced pluripotent stem cells-derived cardiomyocytes. However, the exact biophysical mechanism of this process remains incompletely understood.
To address this, we performed a detailed electrophysiological characterization in a more mature cardiac model, specifically adult mouse ventricular myocytes (AMVMs).
Our in vitro results demonstrate that Ziapin2 can photomodulate cardiac ECC in mature AMVMs without affecting the main transporters and receptors located within the sarcolemma. We established a connection between Ziapin2-induced membrane thickness modulation and light-generated action potentials by showcasing the pivotal role of stretch-activated channels (SACs). Notably, our experimental findings, through pharmacological blockade, suggest that non-selective SACs might serve as the biological culprit responsible for the effect.
Taken together, these findings elucidate the intricacies of Ziapin2-mediated photostimulation mechanism and open new perspectives for its application in cardiac research.
利用光来控制活细胞的活动是心脏研究中很有前途的一种方法，因为它具有无与伦比的时空选择性和最小的侵入性。Ziapin2 是一种新合成的偶氮苯化合物，最近被报道为一种有效的工具，用于光驱动调节人诱导多能干细胞衍生的心肌细胞中的兴奋-收缩偶联（ECC）。然而，这个过程的确切生物物理机制仍不完全清楚。
为了解决这个问题，我们在一个更成熟的心脏模型中，即成年小鼠心室肌细胞（AMVMs）中进行了详细的电生理学特征描述。
我们的体外结果表明，Ziapin2 可以在不影响位于肌膜内的主要转运体和受体的情况下，光调制成熟的 AMVMs 中的心脏 ECC。我们通过展示拉伸激活通道（SACs）的关键作用，建立了 Ziapin2 诱导的膜厚度调制与光产生动作电位之间的联系。值得注意的是，我们的实验结果通过药理学阻断表明，非选择性 SACs 可能是导致这种效应的生物学罪魁祸首。
总之，这些发现阐明了 Ziapin2 介导的光刺激机制的复杂性，并为其在心脏研究中的应用开辟了新的视角。
