Cardiac myosin isoforms from different species have unique enzymatic and mechanical properties.
The mammalian heart contains two cardiac myosin isoforms: beta-myosin heavy chain (MHC) is found predominantly in the ventricles of large mammals, and alpha-MHC is expressed in the atria. The sequence identity between these isoforms is approximately 93%, with nonidentical residues clustered in discrete, functionally important domains associated with actin binding and ATPase activity. It is well-established that rabbit alpha-cardiac myosin has a 2-fold greater unloaded shortening velocity than beta-cardiac myosin but a 2-fold lower average isometric force. Here, we test the generality of these relationships for another large mammal, the pig, as well as for a small rodent, the mouse, which expresses alpha-MHC in its ventricles throughout adulthood. Hydrophobic interaction chromatography (HIC) was used to purify myosin from mouse, rabbit, and pig hearts. The superior resolving power of HIC made it possible to prepare highly homogeneous, enzymatically active myosin from small amounts of tissue. The movement of actin filaments by myosin was measured in an in vitro motility assay. The same assay could be used to determine average isometric force by loading the actin filaments with increasing concentrations of alpha-actinin to stop filament motion. We conclude that myosin from the mouse has significantly higher velocities for both alpha and beta isoforms than myosin from rabbits and pigs, even though the 2-fold difference in velocity between isoforms is maintained. Unlike the larger mammals, however, the small rodent generates the same high isometric force for both alpha and beta isoforms. Thus, nature has adapted the function of cardiac myosin isoforms to optimize power output for hearts of a given species.
Malmqvist
Ulf P
UP
Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont 05405-0068, USA.
Aronshtam
Alexander
A
Lowey
Susan
S
D000199:Actins / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D024743:Atrial Myosins / Q000737:chemistry / Q000378:metabolism; D001696:Biomechanical Phenomena; D024722:Cardiac Myosins / Q000032:analysis* / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000502:physiology; D020033:Protein Isoforms / Q000502:physiology*; D011817:Rabbits; D013045:Species Specificity; D013552:Swine; D024723:Ventricular Myosins / Q000737:chemistry / Q000378:metabolism
D000199:Actins; D020033:Protein Isoforms; D000251:Adenosine Triphosphatases; D024743:Atrial Myosins; D024722:Cardiac Myosins; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains