Lys184 deletion in troponin I impairs relaxation kinetics and induces hypercontractility in murine cardiac myofibrils

Abstract

We conclude that these changes are not due to alterations of the intrinsic cross-bridge kinetics. The molecular mechanism of sarcomeric diastolic dysfunction in this FHC model is based on the impaired regulatory switch-off kinetics of cTnI, which induces incomplete inhibition of force-generating cross-bridges at low [Ca(2+)] and thereby slows down relaxation of sarcomeres. Ca(2+) sensitization and impairment of the relaxation of sarcomeres induced by this mutation may underlie the enhanced systolic function and diastolic dysfunction at the sarcomeric level.