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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents



ID: 474479.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Impulse conduction and gap junctional remodelling by endothelin-1 in cultured neonatal rat ventricular myocytes
Authors:Reisner, Y.; Meiry, G.; Zeevi-Levin, N.; Barac, D. Y.; Reiter, I.; Abassi, Z.; Ziv, N.; Kostin, S.; Schaper, J.; Rosen, M. R.; Binah, O.
Date of Publication (YYYY-MM-DD):2009
Title of Journal:J Cell Mol Med
Volume:13
Issue / Number:3
Start Page:562
End Page:73
Audience:Not Specified
Abstract / Description:Endothelin-1 (ET-1) is an important contributor to ventricular hypertrophy and failure, which are associated with arrhythmogenesis and sudden death. To elucidate the mechanism(s) underlying the arrhythmogenic effects of ET-1 we tested the hypothesis that long-term (24 hrs) exposure to ET-1 impairs impulse conduction in cultures of neonatal rat ventricular myocytes (NRVM). NRVM were seeded on micro-electrode-arrays (MEAs, Multi Channel Systems, Reutlingen, Germany) and exposed to 50 nM ET-1 for 24 hrs. Hypertrophy was assessed by morphological and molecular methods. Consecutive recordings of paced activation times from the same cultures were conducted at baseline and after 3, 6 and 24 hrs, and activation maps for each time period constructed. Gap junctional Cx43 expression was assessed using Western blot and confocal microscopy of immunofluorescence staining using anti-Cx43 antibodies. ET-1 caused hypertrophy as indicated by a 70% increase in mRNA for atrial natriuretic peptide (P < 0.05), and increased cell areas (P < 0.05) compared to control. ET-1 also caused a time-dependent decrease in conduction velocity that was evident after 3 hrs of exposure to ET-1, and was augmented at 24 hrs, compared to controls (P < 0.01). ET-1 increased total Cx43 protein by approximately 40% (P < 0.05) without affecting non- phosphorylated Cx43 (NP-Cx43) protein expression. Quantitative confocal microscopy showed a approximately 30% decrease in the Cx43 immunofluorescence per field in the ET-1 group (P < 0.05) and a reduced field stain intensity (P < 0.05), compared to controls. ET-1-induced hypertrophy was accompanied by reduction in conduction velocity and gap junctional remodelling. The reduction in conduction velocity may play a role in ET-1 induced susceptibility to arrhythmogenesis.
Free Keywords:Animals; Animals, Newborn; Cardiomegaly/pathology/physiopathology; Cells, Cultured; Connexin 43/metabolism; Endothelin-1/*pharmacology; Gap Junctions/*drug effects/*metabolism; Heart Conduction System/*drug effects/physiopathology; Heart Ventricles/*cytology/drug effects/pathology/physiopathology; Myocytes, Cardiac/*drug effects/*metabolism/pathology; Rats; Rats, Sprague-Dawley
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Rappaport Family Institute for Research in the Medical Sciences, Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Identifiers:ISSN:1582-4934 (Electronic) 1582-1838 (Linking)
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=..
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