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

ID: 428370.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Impulse conduction and gap junctional remodeling 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.; Shaper, J.; Rosen, M. R.; Binah, O.
Date of Publication (YYYY-MM-DD):2008
Title of Journal:J Cell Mol Med
Audience:Not Specified
Abstract / Description:Objective: 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). Methods: NRVM were seeded on Micro-Electrode-Arrays (MEAs, Multi Channel Systems) 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. Results: ET-1 caused hypertrophy as indicated by a 70% increase in mRNA for atrial natriuretic peptide (ANP, 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/field in the ET-1 group (P<0.05) and a reduced field stain intensity (p<0.05), compared to controls. Conclusion: ET-1-induced hypertrophy is accompanied by reduction in conduction velocity and gap junctional remodeling. The reduction in conduction velocity may play a role in ET-1 induced susceptibility to arrhythmogenesis.
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
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