| Calmodulin kinase II activity is required for normal atrioventricular nodal conduction. | |
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MedLine Citation:
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PMID: 15922273 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is abundant in myocardium. CaMKII activity is augmented by catecholamine stimulation, which enhances AV nodal conduction, suggesting the hypothesis that CaMKII also contributes to AV nodal conduction properties. OBJECTIVES: The purpose of this study was to test the potential role of CaMKII in regulating AV nodal conduction in heart. METHODS: We developed a novel mouse with genetic CaMKII inhibition by cardiac-specific expression of autocamtide 3 inhibitory peptide (AC3-I) mimicking a conserved sequence of the CaMKII regulatory domain. We also engineered a control transgenic mouse with cardiac expression of an inactive, scrambled version of AC3-I (autocamtide 3 control peptide [AC3-C]) and performed electrophysiologic measurements in vivo and in Langendorff-perfused isolated hearts. RESULTS: AC3-I and AC3-C were abundantly expressed in AV nodal cells. AC3-I mice with implanted ECG telemeters showed enhanced Wenckebach-type AV conduction block after isoproterenol (present in 9/9 mice) compared with AC3-C mice (present in 1/5 mice, P = .005). Intracardiac recordings showed significant PR and AH interval prolongation in AC3-I mice at baseline and after isoproterenol compared with AC3-C mice. HV durations were not different. Langendorff-perfused AC3-I hearts had significantly prolonged Wenckebach cycle lengths and AV nodal effective refractory periods compared with AC3-C hearts, whereas sinus node recovery time and left ventricular effective refractory times were similar between these genotypes. CONCLUSIONS: These studies define CaMKII as a critical determinant of normal and catecholamine-stimulated AV nodal conduction responses. |
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Authors:
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Michelle S C Khoo; Prince J Kannankeril; Jingdong Li; Rong Zhang; Sabina Kupershmidt; Wei Zhang; James B Atkinson; Roger J Colbran; Dan M Roden; Mark E Anderson |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Heart rhythm : the official journal of the Heart Rhythm Society Volume: 2 ISSN: 1547-5271 ISO Abbreviation: Heart Rhythm Publication Date: 2005 Jun |
Date Detail:
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Created Date: 2005-05-30 Completed Date: 2005-10-04 Revised Date: 2009-10-27 |
Medline Journal Info:
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Nlm Unique ID: 101200317 Medline TA: Heart Rhythm Country: United States |
Other Details:
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Languages: eng Pagination: 634-40 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Vanderbilt University Medical School, Nashville, Tennessee 37232-6300, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Atrioventricular Node / physiology* Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases / physiology* Gene Expression Regulation, Enzymologic Mice Mice, Transgenic Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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HL03727/HL/NHLBI NIH HHS; HL62494/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 2; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinases |
| Comments/Corrections | |
Comment In:
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Heart Rhythm. 2005 Jun;2(6):641-2
[PMID:
15922274
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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