Decreased ATPase Activity and Increased Calcium Sensitivity in Myofibrils with E180G a-Tropomyosin Missense Mutation Causing Familial Hypertrophic Cardiomyopathy
MetadataShow full item record
Heart disease is a common affliction that affects the quality of life and is the leading cause of death in the US. Familial hypertrophic cardiomyopathy (FHC) is caused by several mutations, some of which occur in α-tropomyosin. Tropomyosin is an integral contractile protein of the sarcomere, which is the functional unit of the heart that regulates its contractions and therefore affects heart contractility when mutated. E180G is one such point mutation that improves systolic function while impairing diastolic function, which causes the heart to hypertrophy and can lead to sudden death. This study, the first of its kind, focused on the ATPase activity and calcium sensitivity of cardiac myofibrils regulated by the α-tropomyosin E180G mutation as compared to non-transgenic (NTG) α-tropomyosin. ATPase assays were performed on myofibril samples prepared from mice hearts to quantify the number of contractions in a sarcomere. Calcium sensitivity was explored to determine how the E180G mutation disturbs the cardiac cycle. The results were consistent with previous expectations that the E180G mutation would decrease ATPase activity and increase calcium sensitivity when compared to a NTG control. Decreased ATPase activity demonstrated reduced heart contractions and the increased calcium sensitivity revealed the relation between calcium and altered diastole that causes the heart to overwork and result in hypertrophy. As heart disease is less prevalent in women, future work should focus on sex-related differences and the cardioprotective effects that estrogen could impart on E180G mutants. Targeting calcium regulation with therapeutic drugs would also be a viable path for future research of FHC, as it plays a vital role in the cardiac cycle.