| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Physiology and Biophysics Unit, University of Muenster, Muenster, Germany
2 German Center for Fetal Surgery & Minimally-Invasive Therapy, University of Bonn, Bonn, Germany
* To whom correspondence should be addressed. E-mail: wlinke{at}uni-muenster.de.
The giant protein titin, a major contributor to myocardial mechanics, is expressed in two main cardiac isoforms: stiff N2B (3.0MDa) and more compliant N2BA (>3.2MDa). Fetal hearts of mice, rats, and pigs express a unique N2BA-isoform (~3.7MDa) 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 mid-gestation. 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-pig, and adult rat. However, only ~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 ssTnI was replaced by adult cTnI shortly after birth, thereby reducing the Ca2+-sensitivity of force development. In contrast, guinea-pig and sheep co-expressed 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-specifically regulated, events.
This article has been cited by other articles:
|
|
 |
|
  W. A. Linke Sense and stretchability: The role of titin and titin-associated proteins in myocardial stress-sensing and mechanical dysfunction Cardiovasc Res, March 1, 2008; 77(4): 637 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kruger, C. Sachse, W. H. Zimmermann, T. Eschenhagen, S. Klede, and W. A. Linke Thyroid Hormone Regulates Developmental Titin Isoform Transitions via the Phosphatidylinositol-3-Kinase/ AKT Pathway Circ. Res., February 29, 2008; 102(4): 439 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. P. Shapiro, C. S.P. Lam, J. B. Patel, S. F. Mohammed, M. Kruger, D. M. Meyer, W. A. Linke, and M. M. Redfield Acute and Chronic Ventricular-Arterial Coupling in Systole and Diastole: Insights From an Elderly Hypertensive Model Hypertension, September 1, 2007; 50(3): 503 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. P. de Tombe, A. Belus, N. Piroddi, B. Scellini, J. S. Walker, A. F. Martin, C. Tesi, and C. Poggesi Myofilament calcium sensitivity does not affect cross-bridge activation-relaxation kinetics Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2007; 292(3): R1129 - R1136. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
