Key result
The R403Q mutation accelerated tension generation and relaxation in human cardiac myofibrils compared to a healthy control, leading to an apparent gain of protein function but greater energetic cost.
Why the study?
Does the R403Q mutation alter contraction and relaxation mechanics in human cardiac myofibrils compared to healthy controls?
Does the R403Q mutation alter contraction and relaxation mechanics in human cardiac myofibrils compared to healthy controls?
The R403Q mutation in familial hypertrophic cardiomyopathy causes faster tension generation and relaxation but at a greater energetic cost, which may be central to the disease process.
Should not change clinical practice in HCM; leaves open whether energetic modulation alters R403Q disease progression.
The R403Q mutation in beta-myosin heavy chain was the first mutation to be identified as responsible for familial hypertrophic cardiomyopathy (FHC). In spite of extensive work on the functional sequelae of this mutation, the mechanism by which the mutant protein causes the disease has not been definitely identified. Here we directly compare contraction and relaxation mechanics of single myofibrils from left ventricular samples of one patient carrying the R403Q mutation to those from a healthy control heart. Tension generation and relaxation following sudden increase and decrease in [Ca(2+)] were much faster in the R403Q myofibrils with relaxation rates being the most affected parameters. The results show that the R403Q mutation leads to an apparent gain of protein function but a greater energetic cost of tension generation. Increased energy cost of tension generation may be central to the FHC disease process, help explain some unresolved clinical observations, and carry significant therapeutic implications.
No takes yet. Share an insight, caveat, or question.
Belus et al. (2008) studied Familial hypertrophic cardiomyopathy (n=2). R403Q mutation vs. Healthy control heart was evaluated on Contraction and relaxation mechanics of single myofibrils. The R403Q mutation accelerated tension generation and relaxation in human cardiac myofibrils compared to a healthy control, leading to an apparent gain of protein function but greater energetic cost.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: