%0 Journal Article %1 Palmer2004 %A Palmer, B. M. %A Fishbaugher, D. E. %A Schmitt, J. P. %A Wang, Y. %A Alpert, N. R. %A Seidman, C. E. %A Seidman, J. G. %A VanBuren, P. %A Maughan, D. W. %D 2004 %J Am J Physiol Heart Circ Physiol %K *Heterozygote *Mutation, *Myocardial *Point Actins/metabolism Activation Adenosine Animals Arginine/genetics Calcium/metabolism Cardiomyopathy, Chains/*genetics/metabolism Contraction Cysteine/genetics Enzyme Factors Glutamine/genetics Heavy Hypertrophic/*genetics/metabolism/physiopathology Isometric Kinetics Male Mice Missense Mutation Myocardium/metabolism Myosin Myosins/*genetics/metabolism Time Triphosphatases/metabolism Ventricular %N 1 %P H91-9 %T Differential cross-bridge kinetics of FHC myosin mutations R403Q and R453C in heterozygous mouse myocardium %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15001446 %V 287 %X The kinetic effects of the cardiac myosin point mutations R403Q and R453C, which underlie lethal forms of familial hypertrophic cardiomyopathy (FHC), were assessed using isolated myosin and skinned strips taken from heterozygous (R403Q/+ and R453C/+) male mouse hearts. Compared with wild-type (WT) mice, actin-activated ATPase was increased by 38% in R403Q/+ and reduced by 45% in R453C/+, maximal velocity of regulated thin filament (V(RTF)) in the in vitro motility assay was increased by 8% in R403Q/+ and was not different in R453C/+, myosin concentration at half-maximal V(RTF) was reduced by 30% in R403Q/+ and not different in R453C/+, and the characteristic frequency for oscillatory work production (b frequency), determined by sinusoidal analysis in the skinned strip at maximal calcium activation, was 27% lower in R403Q/+ and 18% higher in R453C/+. The calcium sensitivity for isometric tension in the skinned strip was not different in R403Q/+ (pCa(50) 5.64 +/- 0.02) and significantly enhanced in R453C/+ (5.82 +/- 0.03) compared with WT (5.58 +/- 0.02). We conclude that isolated myosin and skinned strips of R403Q/+ and R453C/+ myocardium show marked differences in cross-bridge kinetic parameters and in calcium sensitivity of force production that indicate different functional roles associated with the location of each point mutation at the molecular level.

@article{Palmer2004, abstract = {The kinetic effects of the cardiac myosin point mutations R403Q and R453C, which underlie lethal forms of familial hypertrophic cardiomyopathy (FHC), were assessed using isolated myosin and skinned strips taken from heterozygous (R403Q/+ and R453C/+) male mouse hearts. Compared with wild-type (WT) mice, actin-activated ATPase was increased by 38% in R403Q/+ and reduced by 45% in R453C/+, maximal velocity of regulated thin filament (V(RTF)) in the in vitro motility assay was increased by 8% in R403Q/+ and was not different in R453C/+, myosin concentration at half-maximal V(RTF) was reduced by 30% in R403Q/+ and not different in R453C/+, and the characteristic frequency for oscillatory work production (b frequency), determined by sinusoidal analysis in the skinned strip at maximal calcium activation, was 27% lower in R403Q/+ and 18% higher in R453C/+. The calcium sensitivity for isometric tension in the skinned strip was not different in R403Q/+ (pCa(50) 5.64 +/- 0.02) and significantly enhanced in R453C/+ (5.82 +/- 0.03) compared with WT (5.58 +/- 0.02). We conclude that isolated myosin and skinned strips of R403Q/+ and R453C/+ myocardium show marked differences in cross-bridge kinetic parameters and in calcium sensitivity of force production that indicate different functional roles associated with the location of each point mutation at the molecular level.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Palmer, B. M. and Fishbaugher, D. E. and Schmitt, J. P. and Wang, Y. and Alpert, N. R. and Seidman, C. E. and Seidman, J. G. and VanBuren, P. and Maughan, D. W.}, biburl = {https://www.bibsonomy.org/bibtex/2273bf3698ee50f6cae390d27caf68071/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {f91a3d6721950a5e853b4927a09dac9c}, intrahash = {273bf3698ee50f6cae390d27caf68071}, issn = {0363-6135 (Print) 0363-6135 (Linking)}, journal = {Am J Physiol Heart Circ Physiol}, keywords = {*Heterozygote *Mutation, *Myocardial *Point Actins/metabolism Activation Adenosine Animals Arginine/genetics Calcium/metabolism Cardiomyopathy, Chains/*genetics/metabolism Contraction Cysteine/genetics Enzyme Factors Glutamine/genetics Heavy Hypertrophic/*genetics/metabolism/physiopathology Isometric Kinetics Male Mice Missense Mutation Myocardium/metabolism Myosin Myosins/*genetics/metabolism Time Triphosphatases/metabolism Ventricular}, month = Jul, note = {Palmer, Bradley M Fishbaugher, David E Schmitt, Joachim P Wang, Yuan Alpert, Norman R Seidman, Christine E Seidman, J G VanBuren, Peter Maughan, David W HL-59408-3/HL/NHLBI NIH HHS/United States In Vitro Research Support, U.S. Gov't, P.H.S. United States American journal of physiology. Heart and circulatory physiology Am J Physiol Heart Circ Physiol. 2004 Jul;287(1):H91-9. Epub 2004 Mar 4.}, number = 1, pages = {H91-9}, shorttitle = {Differential cross-bridge kinetics of FHC myosin mutations R403Q and R453C in heterozygous mouse myocardium}, timestamp = {2010-12-14T18:12:28.000+0100}, title = {Differential cross-bridge kinetics of FHC myosin mutations R403Q and R453C in heterozygous mouse myocardium}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15001446}, volume = 287, year = 2004 }