Developmental changes in passive stiffness and myofilament Ca2+sensitivity due to titin and troponin-I isoform switching are not critically triggered by birth
- 1 August 2006
- journal article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 291 (2), H496-H506
- https://doi.org/10.1152/ajpheart.00114.2006
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 (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 STpwere estimated in force measurements on skinned cardiac muscle strips by selective titin proteolysis, leaving the collagen matrix unaffected. Titin-based STpcontributed between 42% and 58% to total STpin late-fetal and adult sheep/guinea pigs and adult rats. However, only ∼20% of total STpwas titin based in late-fetal rat. Titin-borne passive tension and the proportion of titin-based STpgenerally 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.Keywords
This publication has 53 references indexed in Scilit:
- Coupled expression of troponin T and troponin I isoforms in single skeletal muscle fibers correlates with contractilityAmerican Journal of Physiology-Cell Physiology, 2006
- A Novel Marker for Vertebrate Embryonic Heart, the EH-myomesin IsoformPublished by Elsevier BV ,2000
- Inotropic effects of ryanodine and nicardipine on fetal, neonatal and adult guinea-pig myocardiumEuropean Journal of Pharmacology, 1994
- Differential Regulation of Slow-skeletal and Cardiac Troponin I mRNA during Development and by Thyroid Hormone in Rat HeartJournal of Molecular and Cellular Cardiology, 1994
- Expression of the sarcomeric actin isogenes in the rat heart with development and senescence.Circulation Research, 1992
- Developmental expression of troponin I isoforms in fetal human heartFEBS Letters, 1991
- Effect of thyroid status on thin-filament Ca2+ regulation and expression of troponin I in perinatal and adult rat hearts.Circulation Research, 1990
- Shortening velocity and myosin and myofibrillar ATPase activity related to myosin isoenzyme composition during postnatal development in rat myocardium.Circulation Research, 1989
- Biophysics of the developing heartAmerican Journal of Obstetrics and Gynecology, 1982
- CALCIUM‐INDUCED RELEASE OF CALCIUM FROM THE SARCOPLASMIC RETICULUM OF SKINNED CELLS FROM ADULT HUMAN, DOG, CAT, RABBIT, RAT, AND FROG HEARTS AND FROM FETAL AND NEW‐BORN RAT VENTRICLES*Annals of the New York Academy of Sciences, 1978