In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 291, No. 2 ( 2006-08), p. H496-H506
Abstract:
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 (∼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 (ST p ) 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 ST p were estimated in force measurements on skinned cardiac muscle strips by selective titin proteolysis, leaving the collagen matrix unaffected. Titin-based ST p contributed between 42% and 58% to total ST p in late-fetal and adult sheep/guinea pigs and adult rats. However, only ∼20% of total ST p was titin based in late-fetal rat. Titin-borne passive tension and the proportion of titin-based ST p 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 Ca 2+ 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 Ca 2+ 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.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.00114.2006
Language:
English
Publisher:
American Physiological Society
Publication Date:
2006
detail.hit.zdb_id:
1477308-9
SSG:
12
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