The HCM-Associated Cardiac Troponin T Mutation K273N Accelerates Tension Generation and Relaxation in Human Cardiac Myofibrils

In spite of extensive work on the functional sequelae of Hypertrophic CardioMyopathy (HCM)-associated mutations in sarcomeric proteins, the mechanisms by which the mutant proteins cause the disease have not been definitely identified. Here we use the single myofibril technique (Tesi et al., Biophys. J., 2002, 83, 2142-2151) to compare the kinetics of contraction and relaxation of myofibrils isolated from frozen left ventricular samples of one homozygous HCM patient carrying the cardiac Troponin T (cTnT) mutation K273N (underwent heart transplantation) to those from “control” hearts. Preparations, mounted in a force recording apparatus (15 °C), were maximally Ca2+-activated (pCa 4.5) and fully relaxed (pCa 9) by rapid (