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  • Print publication year: 1998
  • Online publication date: May 2010

3 - Development of the myocardial contractile system

from Part I - Molecular, cellular, and integrative mechanisms determining cardiovascular development

Summary

During the course of maturation the developing heart is subjected to variations in hemodynamic load and in the availability of oxygen and other substrates, so it is not surprising that the constituents responsible for the force generated during myocardial contraction will vary as well. The investigation of contractile protein variation during cardiac development has focused on qualitative and quantitative changes in protein isoforms. Information is also emerging about the regulatory signals that control these processes. However, much remains unknown about the functional consequences of the shifts in cardiac contractile proteins that occur with development. This chapter will outline the developmental changes in the contractile apparatus that mediate the cellular mechanics of contraction.

Mechanisms for diversity in contractile protein isoforms

The protein content of the myofibril in general reflects the transcript levels for individual proteins. Variation in myofibril composition during development is mediated by two mechanisms: alternative splicing of transcripts or differential expression of members of a multigene family (Andreadis, Gallego, & Nadal-Ginard, 1987; Nadal-Ginard et al., 1991; Chien et al., 1993; Sartorelli, Kurabayashi, & Kedes, 1993). For example, alternative splicing of transcripts regulates the troponin T (TnT) isoforms in the developing heart and determines the tissue-specific isoforms of the cc-tropomyosin (a-TM) gene (Nadal-Ginard et al., 1991). The transcriptional regulation of contractile protein genes in the heart is the subject of active investigation. A few general themes have emerged from the study of the transcriptional regulation of these genes. First, although some regulatory elements may be shared between skeletal muscle and heart, the regulatory regions controlling gene expression in heart are often distinct from those regulating expression in skeletal muscle.