Evolution of the regulatory control of the vertebrate heart: The role of the contractile proteins

Abstract

The contraction of the vertebrate heart is initiated when intercellular Ca2+ increases and binds to the contractile element via cardiac troponin C (cTnC). The activation of cTnC triggers a series of conformational changes through the components of the thin filament that results in the generation of force by the myocyte. While all cardiac contractions are powered by this mechanism, comparison of cardiac function between vertebrate species reveals significant variation. This includes differences in heart rate, the strength of contraction as well as in regulatory ability. The purpose of this work is to examine the functional basis for such differences and how these have evolved within the vertebrate heart. The function of cardiac troponin I (cTnI) and cardiac myosin-binding protein C (cMyBP-C) and how they are regulated by protein kinase A (PKA) is specifically examined. (PKA is activated within the heart following β-adrenergic stimulation.) The influence of the evolution of endothermy on the function of the contractile element is also considered. This analysis is completed through the integration of a variety of studies that have looked at protein function and contractile function in the hearts of different species as well as studies that have utilized phylogenetic approaches to examine the evolution of specific proteins. It is generally found that as the heart became more complex in both anatomy and functional capacity, changes in protein sequence enabled greater control of the contractile reaction. In addition, the evolution of endothermy appears to have driven changes in the function of specific proteins including cTnC and cTnI.