Semmler, Judith, Kormann, Jan, Srinivasan, Sureshkumar Perumal, Koester, Annette, Saelzer, Daniel, Reppel, Michael, Hescheler, Juergen, Plomann, Markus and Nguemo, Filomain (2018). Pacsin 2 is required for the maintenance of a normal cardiac function in the developing mouse heart. Pharmacol. Res., 128. S. 200 - 211. LONDON: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. ISSN 1043-6618

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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 15.5 days 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 (I-F), as well as L-type Ca2+ channel (I-CaL), and sodium channel (I-Na). 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. (C) 2017 Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Semmler, JudithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kormann, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Srinivasan, Sureshkumar PerumalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koester, AnnetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saelzer, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reppel, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hescheler, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Plomann, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nguemo, FilomainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-196856
DOI: 10.1016/j.phrs.2017.10.004
Journal or Publication Title: Pharmacol. Res.
Volume: 128
Page Range: S. 200 - 211
Date: 2018
Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Place of Publication: LONDON
ISSN: 1043-6618
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PLURIPOTENT STEM-CELLS; RECYCLING ENDOSOMES; PACEMAKER ACTIVITY; DOMAIN PROTEINS; CALCIUM CURRENT; TRAFFICKING; MODULATION; CONDUCTION; EXPRESSION; MIGRATIONMultiple languages
Pharmacology & PharmacyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/19685

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