Cardiotonic bipyridine amrinone slows myosin-induced actin filament sliding at saturating [MgATP]
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/305224
- author
- Klinth, J ; Arner, Anders LU and Mansson, A
- organization
- publishing date
- 2003
- 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
- 10.1023/A:1024894130989
- language
- English
- LU publication?
- yes
- id
- 0fa2a6d5-976b-41d5-87d0-6b5f02df3cf8 (old id 305224)
- date added to LUP
- 2016-04-01 16:34:45
- date last changed
- 2022-01-28 20:39:30
@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 >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.}},
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/10.1023/A:1024894130989}},
doi = {{10.1023/A:1024894130989}},
volume = {{24}},
year = {{2003}},
}