Advanced

Cardiac myosin isoforms from different species have unique enzymatic and mechanical properties

Malmqvist, Ulf LU ; Aronshtam, Alexander and Lowey, Susan (2004) In Biochemistry 43(47). p.15058-15065
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemistry
volume
43
issue
47
pages
15058 - 15065
publisher
The American Chemical Society
external identifiers
  • pmid:15554713
  • scopus:9744230560
ISSN
0006-2960
DOI
10.1021/bi0495329
language
English
LU publication?
no
id
714e6c5d-ac7e-4675-9022-4cf29502e097 (old id 1130886)
date added to LUP
2008-06-16 16:33:13
date last changed
2017-07-30 03:35:41
@article{714e6c5d-ac7e-4675-9022-4cf29502e097,
  abstract     = {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.},
  author       = {Malmqvist, Ulf and Aronshtam, Alexander and Lowey, Susan},
  issn         = {0006-2960},
  language     = {eng},
  number       = {47},
  pages        = {15058--15065},
  publisher    = {The American Chemical Society},
  series       = {Biochemistry},
  title        = {Cardiac myosin isoforms from different species have unique enzymatic and mechanical properties},
  url          = {http://dx.doi.org/10.1021/bi0495329},
  volume       = {43},
  year         = {2004},
}