Towards Understanding Mechanisms of Drug Action and Functions of the Body on the Molecular Level. Molecular mechanisms of calcium regulation of striated muscle contraction and its genetic disorder.

Contraction of skeletal and cardiac muscles is regulated by Ca2+ through a specific Ca(2+)-receptive protein, troponin, regularly distributed along the thin filaments. This protein consists of three different subunits, troponins C, I and T. In this article, studies on the structural and biochemical aspects of the molecular mechanisms of Ca(2+)-regulation were first reviewed with particular reference to the regulatory role of troponin T. Several properties of the isoforms of troponin from fast and slow skeletal and cardiac muscles were discussed, based on the findings obtained by the use of troponin-exchange techniques under physiological conditions. Recent findings on the functional consequence of mutations in human cardiac troponins T and I found in familial hypertrophic cardiomyopathy were also presented. The results clarified the increase in Ca(2+)-sensitivity of contraction to be the critical consequence due to this genetic disorder.