| Developmental changes in passive stiffness and myofilament Ca2+ sensitivity due to titin and troponin-I isoform switching are not critically triggered by birth. | |
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MedLine Citation:
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PMID: 16679402 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The giant protein titin, a major contributor to myocardial mechanics, is expressed in two main cardiac isoforms: stiff N2B (3.0 MDa) and more compliant N2BA (>3.2 MDa). Fetal hearts of mice, rats, and pigs express a unique N2BA isoform ( approximately 3.7 MDa) but no N2B. Around birth the fetal N2BA titin is replaced by smaller-size N2BA isoforms and N2B, which predominates in adult hearts, stiffening their sarcomeres. Here we show that perinatal titin-isoform switching and corresponding passive stiffness (STp) changes do not occur in the hearts of guinea pig and sheep. In these species the shift toward "adult" proportions of N2B isoform is almost completed by midgestation. The relative contributions of titin and collagen to STp were estimated in force measurements on skinned cardiac muscle strips by selective titin proteolysis, leaving the collagen matrix unaffected. Titin-based STp contributed between 42% and 58% to total STp in late-fetal and adult sheep/guinea pigs and adult rats. However, only approximately 20% of total STp was titin based in late-fetal rat. Titin-borne passive tension and the proportion of titin-based STp generally scaled with the N2B isoform percentage. The titin isoform transitions were correlated to a switch in troponin-I (TnI) isoform expression. In rats, fetal slow skeletal TnI (ssTnI) was replaced by adult carciac TnI (cTnI) shortly after birth, thereby reducing the Ca2+ sensitivity of force development. In contrast, guinea pig and sheep coexpressed ssTnI and cTnI in fetal hearts, and skinned fibers from guinea pig showed almost no perinatal shift in Ca2+ sensitivity. We conclude that TnI-isoform and titin-isoform switching and corresponding functional changes during heart development are not initiated by birth but are genetically programmed, species-specific regulated events. |
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Authors:
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Martina Krüger; Thomas Kohl; Wolfgang A Linke |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-05-05 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 291 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2006 Aug |
Date Detail:
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Created Date: 2006-07-14 Completed Date: 2006-08-18 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H496-506 Citation Subset: IM |
Affiliation:
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Physiology and Biophysics Unit, Univ. of Muenster, Schlossplatz 5, D-48149 Muenster, Germany. wlinke@uni-muenster.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Blotting, Western Calcium / physiology* Collagen / metabolism Electrophoresis, Polyacrylamide Gel Female Guinea Pigs Heart / growth & development*, physiology* Isomerism Microfilaments / physiology* Microscopy, Electron, Transmission Muscle Proteins / metabolism, physiology* Myocardial Contraction / physiology Myocardium / cytology, metabolism, ultrastructure Myocytes, Cardiac / physiology, ultrastructure Parturition / physiology* Pregnancy Protein Kinases / metabolism, physiology* Rats Rats, Sprague-Dawley Sheep Troponin I / metabolism, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Muscle Proteins; 0/Troponin I; 0/connectin; 7440-70-2/Calcium; 9007-34-5/Collagen; EC 2.7.-/Protein Kinases |
| Comments/Corrections | |
Erratum In:
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Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H726 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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