First Author | Semmler J | Year | 2018 |
Journal | Pharmacol Res | Volume | 128 |
Pages | 200-210 | PubMed ID | 29107716 |
Mgi Jnum | J:276621 | Mgi Id | MGI:6296468 |
Doi | 10.1016/j.phrs.2017.10.004 | Citation | Semmler J, et al. (2018) Pacsin 2 is required for the maintenance of a normal cardiac function in the developing mouse heart. Pharmacol Res 128:200-210 |
abstractText | The Pacsin proteins (Pacsin 1, 2 and 3) play an important role in intracellular trafficking and thereby signal transduction in many cells types. This study was designed to examine the role of Pacsin 2 in cardiac development and function. We investigated the development and electrophysiological properties of Pacsin 2 knockout (P2KO) hearts and single cardiomyocytes isolated from 11.5 and 15.5days old fetal mice. Immunofluorescence experiments confirmed the lack of Pacsin 2 protein expression in P2KO cardiac myocytes in comparison to wildtype (WT). Western blotting demonstrates low expression levels of connexin 43 and T-box 3 proteins in P2KO compared to wildtype (WT). Electrophysiology measurements including online Multi-Electrode Array (MEA) based field potential (FP) recordings on isolated whole heart of P2KO mice showed a prolonged AV-conduction time. Patch clamp measurements of P2KO cardiomyocytes revealed differences in action potential (AP) parameters and decreased pacemaker funny channel (If), as well as L-type Ca(2+) channel (ICaL), and sodium channel (INa). These findings demonstrate that Pacsin 2 is necessary for cardiac development and function in mouse embryos, which will enhance our knowledge to better understand the genesis of cardiovascular diseases. |