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Cardiotonic bipyridine amrinone slows myosin-induced actin filament sliding at saturating [MgATP]

Klinth, J; Arner, Anders LU and Mansson, A (2003) In Journal of Muscle Research and Cell Motility 24(1). p.15-32
Abstract
Previously reported effects of amrinone on skeletal muscle function suggest that the drug reduces the rate constant of myosin cross-bridge dissociation. We have used the in vitro motility assay to further elucidate the mechanism underlying this effect and to aid these studies a new, improved,. lament tracking software was developed in the Matlab(TM) environment. The experiments were carried out at 30degreesC using heavy meromyosin from fast rabbit muscle and rhodamine-phalloidin labeled actin. laments. A slowing effect of amrinone on. lament sliding velocity at 1 mM MgATP was observed at drug concentrations >0.3 mM. This effect showed signs of saturation at the highest drug concentrations (1-2 mM) that could be readily tested. The... (More)
Previously reported effects of amrinone on skeletal muscle function suggest that the drug reduces the rate constant of myosin cross-bridge dissociation. We have used the in vitro motility assay to further elucidate the mechanism underlying this effect and to aid these studies a new, improved,. lament tracking software was developed in the Matlab(TM) environment. The experiments were carried out at 30degreesC using heavy meromyosin from fast rabbit muscle and rhodamine-phalloidin labeled actin. laments. A slowing effect of amrinone on. lament sliding velocity at 1 mM MgATP was observed at drug concentrations >0.3 mM. This effect showed signs of saturation at the highest drug concentrations (1-2 mM) that could be readily tested. The sliding velocity exhibited hyperbolic dependence on [ MgATP] with a V-max of 7.2 +/- 0.9 mum/s and a K-M of 0.18 +/- 0.02 mM. Amrinone (1 mM) reduced V-max by 32 +/- 5% (P < 0.01) and K-M by 42 &PLUSMN; 8% (P < 0.05; n = 4). These results are accounted for in the most straightforward way by a model where amrinone acts directly on the actomyosin system and reduces the rate constant of MgADP release. Such a well-defined effect on the myosin cross-bridge cycle makes the drug a potentially useful pharmacological tool for further studies of myosin function both in vitro and in the ordered. lament array of a living muscle fiber. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Muscle Research and Cell Motility
volume
24
issue
1
pages
15 - 32
publisher
Springer
external identifiers
  • wos:000184336500004
  • pmid:12953834
  • scopus:0042929855
ISSN
0142-4319
DOI
language
English
LU publication?
yes
id
0fa2a6d5-976b-41d5-87d0-6b5f02df3cf8 (old id 305224)
date added to LUP
2007-09-16 09:40:14
date last changed
2018-05-29 10:09:54
@article{0fa2a6d5-976b-41d5-87d0-6b5f02df3cf8,
  abstract     = {Previously reported effects of amrinone on skeletal muscle function suggest that the drug reduces the rate constant of myosin cross-bridge dissociation. We have used the in vitro motility assay to further elucidate the mechanism underlying this effect and to aid these studies a new, improved,. lament tracking software was developed in the Matlab(TM) environment. The experiments were carried out at 30degreesC using heavy meromyosin from fast rabbit muscle and rhodamine-phalloidin labeled actin. laments. A slowing effect of amrinone on. lament sliding velocity at 1 mM MgATP was observed at drug concentrations &gt;0.3 mM. This effect showed signs of saturation at the highest drug concentrations (1-2 mM) that could be readily tested. The sliding velocity exhibited hyperbolic dependence on [ MgATP] with a V-max of 7.2 +/- 0.9 mum/s and a K-M of 0.18 +/- 0.02 mM. Amrinone (1 mM) reduced V-max by 32 +/- 5% (P &lt; 0.01) and K-M by 42 &amp;PLUSMN; 8% (P &lt; 0.05; n = 4). These results are accounted for in the most straightforward way by a model where amrinone acts directly on the actomyosin system and reduces the rate constant of MgADP release. Such a well-defined effect on the myosin cross-bridge cycle makes the drug a potentially useful pharmacological tool for further studies of myosin function both in vitro and in the ordered. lament array of a living muscle fiber.},
  author       = {Klinth, J and Arner, Anders and Mansson, A},
  issn         = {0142-4319},
  language     = {eng},
  number       = {1},
  pages        = {15--32},
  publisher    = {Springer},
  series       = {Journal of Muscle Research and Cell Motility},
  title        = {Cardiotonic bipyridine amrinone slows myosin-induced actin filament sliding at saturating [MgATP]},
  url          = {http://dx.doi.org/},
  volume       = {24},
  year         = {2003},
}