PMID- 31316392
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 10
DP  - 2019
TI  - AAV9-Mediated Overexpression of TRPM4 Increases the Incidence of Stress-Induced 
      Ventricular Arrhythmias in Mice.
PG  - 802
LID - 10.3389/fphys.2019.00802 [doi]
LID - 802
AB  - Ca(2+) activated non-selective (CAN) cation channels have been described in 
      cardiomyocytes since the advent of the patch clamp technique. It has been 
      hypothesized that this type of ion channel contributes to the triggering of 
      cardiac arrhythmias. TRPM4 is to date the only molecular candidate for a CAN 
      cation channel in cardiomyocytes. Its significance for arrhythmogenesis in living 
      animals remains, however, unclear. In this study, we have tested whether 
      increased expression of wild-type (WT) TRPM4 augments the risk of arrhythmias in 
      living mice. Overexpression of WT TRPM4 was achieved via tail vein injection of 
      adeno-associated viral vector serotype 9 (AAV9) particles, which have been 
      described to be relatively cardiac specific in mice. Subsequently, we performed 
      ECG-measurements in freely moving mice to determine their in vivo cardiac 
      phenotype. Though cardiac muscle was transduced with TRPM4 viral particles, the 
      majority of viral particles accumulated in the liver. We did not observe any 
      difference in arrhythmic incidents during baseline conditions. Instead, WT mice 
      that overexpress TRPM4 were more vulnerable to develop premature ventricular 
      ectopic beats during exercise-induced beta-adrenergic stress. Conduction 
      abnormalities were rare and not more frequent in transduced mice compare to WT 
      mice. Taken together, we provide evidence that overexpression of TRPM4 increases 
      the susceptibility of living mice to stress-induced arrhythmias.
FAU - Pironet, Andy
AU  - Pironet A
AD  - Laboratory of Ion Channel Research, TRP Research Platform Leuven, VIB Center for 
      Brain and Disease, Department of Cellular and Molecular Medicine, KU Leuven, 
      Leuven, Belgium.
FAU - Syam, Ninda
AU  - Syam N
AD  - Laboratory of Ion Channel Research, TRP Research Platform Leuven, VIB Center for 
      Brain and Disease, Department of Cellular and Molecular Medicine, KU Leuven, 
      Leuven, Belgium.
FAU - Vandewiele, Frone
AU  - Vandewiele F
AD  - Laboratory of Ion Channel Research, TRP Research Platform Leuven, VIB Center for 
      Brain and Disease, Department of Cellular and Molecular Medicine, KU Leuven, 
      Leuven, Belgium.
FAU - Van den Haute, Chris
AU  - Van den Haute C
AD  - Molecular Virology and Gene Therapy, Department of Pharmaceutical and 
      Pharmacological Sciences, KU Leuven, Leuven, Belgium.
FAU - Kerselaers, Sara
AU  - Kerselaers S
AD  - Laboratory of Ion Channel Research, TRP Research Platform Leuven, VIB Center for 
      Brain and Disease, Department of Cellular and Molecular Medicine, KU Leuven, 
      Leuven, Belgium.
FAU - Pinto, Silvia
AU  - Pinto S
AD  - Laboratory of Ion Channel Research, TRP Research Platform Leuven, VIB Center for 
      Brain and Disease, Department of Cellular and Molecular Medicine, KU Leuven, 
      Leuven, Belgium.
FAU - Vande Velde, Greetje
AU  - Vande Velde G
AD  - Biomedical MRI, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
FAU - Gijsbers, Rik
AU  - Gijsbers R
AD  - Molecular Virology and Gene Therapy, Department of Pharmaceutical and 
      Pharmacological Sciences, KU Leuven, Leuven, Belgium.
FAU - Vennekens, Rudi
AU  - Vennekens R
AD  - Laboratory of Ion Channel Research, TRP Research Platform Leuven, VIB Center for 
      Brain and Disease, Department of Cellular and Molecular Medicine, KU Leuven, 
      Leuven, Belgium.
LA  - eng
PT  - Journal Article
DEP - 20190627
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC6610516
OTO - NOTNLM
OT  - AAV9
OT  - TRPM4
OT  - cardiac arrhythmias
OT  - conduction disorders
OT  - ion channels
OT  - telemetry
OT  - triggered activity
EDAT- 2019/07/19 06:00
MHDA- 2019/07/19 06:01
PMCR- 2019/06/27
CRDT- 2019/07/19 06:00
PHST- 2019/03/07 00:00 [received]
PHST- 2019/06/06 00:00 [accepted]
PHST- 2019/07/19 06:00 [entrez]
PHST- 2019/07/19 06:00 [pubmed]
PHST- 2019/07/19 06:01 [medline]
PHST- 2019/06/27 00:00 [pmc-release]
AID - 10.3389/fphys.2019.00802 [doi]
PST - epublish
SO  - Front Physiol. 2019 Jun 27;10:802. doi: 10.3389/fphys.2019.00802. eCollection 
      2019.