Chamber-related variation in phosphorylation state of cardiac troponin revealed by high resolution top-down mass spectrometry

Abstract

Cardiac troponin complex (cTn) is a key regulator of Ca-2+- mediated cross-bridge cycling in cardiac muscle. Post-translational modifications, especially phosphorylation of cTn, are major mechanisms in modulation of contractile function. Two subunits of cTn, cTnI and cTnT, are considered as the "gold standard" protein biomarkers for detecting acute myocardial infarction. Traditionally, the heart is considered homogeneous for analysis of cardiac proteins. However, both functional and morphological variations have been observed in four heart chambers. Herein we have employed high resolution top-down mass spectrometry to examine cTn purified from healthy swine myocardial tissues. Our data showed varied phosphorylation levels in both cTnI and cTnT extracted from four cardiac chambers respectively, which is likely due to the functional and morphological differences.