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          Institute: MPI für experimentelle Medizin     Collection: Molecular Neuroendocrinology     Display Documents



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ID: 292207.0, MPI für experimentelle Medizin / Molecular Neuroendocrinology
Urocortin II enhances contractility in rabbit ventricular myocytes via CRF2 receptor-mediated stimulation of protein kinase A
Authors:Yang, Li-Zhen; Kockskämper, Jens; Heinzel, Frank R.; Hauber, Michael; Walther, Stefanie; Spiess, Joachim; Pieske, Burkert
Language:English
Date of Publication (YYYY-MM-DD):2006-02
Title of Journal:Cardiovascular Research
Journal Abbrev.:Cardiovascular Research
Volume:69
Issue / Number:2
Start Page:402
End Page:411
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Objective: Urocortin II (UcnII), a peptide of the corticotropin-releasing factor (CRF) family, exerts profound actions on the cardiovascular system. Direct effects of UcnII on adult cardiomyocytes have not been evaluated before. Our aim was to characterize functional effects of UcnII on cardiomyocytes and to elucidate the underlying signaling pathway(s) and cellular mechanisms. Methods: Rabbit ventricular cardiomyocytes were stimulated at 0.5 Hz (22-25 degrees C). Unloaded cell shortening (FS, edge detection), [Ca2+](i) transients (Fluo-4), and L-type Ca2+ currents (I-Ca, whole-cell patch clamping) were measured. Sarcoplasmic reticulum (SR) Ca2+ load was assessed by rapid application of caffeine (20 mmol/L). Results: UcnII increased cell shortening and accelerated relaxation in a time- and concentration-dependent manner (EC50: 10.7 nmol/L). The inotropic effect of UcnII was maximal at 100 nmol/L (35% +/- 11% increase in FS, n=8, P<0.05). The inotropic and lusitropic actions of UcnII were largely eliminated by inhibition of CRF2 receptors (10 nmol/L antisauvagine-30, n = 5) or protein kinase A (PKA, 500 nmol/L H-89, n=5). UcnII increased [Ca2+](i) transient amplitude (by 63% +/- 35%, n=7, P<0.05) and decreased the time constant for decay (from 800 +/- 63 to 218 +/- 27 ms, n=7,P<0.001). UcnII also increased SR Ca2+ load (by 19% +/- 7%, n=7,P<0.05) and fractional Ca2+ release (from 57% +/- 7% to 98% +/- 2%, n=7, P<0.01). I-Ca was augmented by 32.7% +/- 10.0% (n=9, P<0.05) and the I-Ca-V relationship was shifted by - 15 mV during UcnII treatment. Conclusion: UcnII exerts positive inotropic and lusitropic effects in cardiomyocytes via CRF2 receptor-mediated stimulation of PKA which augments I-Ca and SR Ca2+ load to increase SR Ca2+ release and [Ca2+](i) transients. (C) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
Free Keywords:peptide hormones; myocytes; e-c coupling; protein kinase A; SR (function) CORTICOTROPIN-RELEASING-FACTOR; HEART-FAILURE; FAMILY; PHOSPHORYLATION; ANTAGONISTS; MODULATION; AFFINITY; TRIGGER; MUSCLE; MEMBER
External Publication Status:published
Document Type:Article
Communicated by:Joachim Spiess
Affiliations:MPI für experimentelle Medizin/Molecular Neuroendocrinology
External Affiliations:Dept. of Cardiology and Pneumology, Georg-August-Universität Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, Germany
Identifiers:ISSN:0008-6363 [ID No:1]
ISI:000235285900014 [ID No:2]
ISI:000235285900014 [ID No:3]
DOI:10.1016/j.cardiores.2005.10.015
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