Pacsin 2 is required for the maintenance of a normal cardiac function in the developing mouse heart

Pharmacol Res. 2018 Feb;128:200-210. doi: 10.1016/j.phrs.2017.10.004. Epub 2017 Oct 28.

Abstract

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 Ca2+ 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.

Keywords: AV conduction; Developing heart; Ion channels; Knockout mouse; Myocardial function; Pacsin 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cytoskeletal Proteins
  • Embryonic Development / physiology*
  • Female
  • Heart / physiology*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proteins / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • Pacsin2 protein, mouse
  • Proteins