E22K mutation of RLC that causes familial hypertrophic cardiomyopathy in heterozygous mouse myocardium: effect on cross-bridge kinetics

Familial hypertrophic cardiomyopathy is a disease characterized by left ventricular and/or septal hypertrophy and myofibrillar disarray. It is caused by mutations in sarcomeric proteins, including the ventricular isoform of myosin regulatory light chain (RLC). The E22K mutation is located in the RLC Ca2+-binding site. We have studied transgenic (Tg) mouse cardiac myofibrils during single-turnover contraction to examine the influence of E22K mutation on 1) dissociation time (τ1) of myosin heads from thin filaments, 2) rebinding time (τ2) of the cross bridges to actin, and 3) dissociation time (τ3) of ADP from the active site of myosin. τ1 was determined from the increase in the rate of rotation of actin monomer to which a cross bridge was bound. τ2 was determined from the rate of anisotropy change of the recombinant essential light chain of myosin labeled with rhodamine exchanged for native light chain (LC1) in the cardiac myofibrils. τ3 was determined from anisotropy of muscle preloaded with a stoichiomet...