Intracellular mechanisms of verapamil and diltiazem action on striated muscle of the rabbit.
Naunyn Schmiedebergs Arch Pharmacol
; 338(3): 297-302, 1988 Sep.
Article
em En
| MEDLINE
| ID: mdl-3194038
ABSTRACT
Skinned fibers from striated muscle were used to study the intracellular mechanisms (contractile proteins and sarcoplasmic reticulum [SR]) of action of diltiazem (DT) and verapamil (VP) on muscle contraction. Rabbit papillary muscle (PM), and the skeletal muscles adductor magnus (AM, fast-twitch) and soleus (SL, slow-twitch) were used. The muscles were skinned by homogenization and fibre bundles for PM and single fibres for AM and SL were dissected from the homogenate and mounted on photodiode force transducers. VP (0.1-3.0 mmol/l) (and to a lesser degree DT) increased Ca2+-activated tension development of the contractile protains in PM and SL and decreased it in AM (+[4-20]%, +4%, -[14-28]%, respectively). Both drugs increased the submaximal Ca2+-activated tension development at the order of PM = SL greater than AM in a dose-dependent manner. The changes of half-maximal pCa50 at 1 mmol/l VP were 0.25, 0.25, and 0.15, respectively. For Ca2+ uptake and release from the SR, VP as well as DT (0.1-3.0 mmol/l) in the uptake phase decreased caffeine-induced tension transients in a dose-dependent fashion. At 0.01-3.0 mmol/l, the drugs directly induced Ca2+ release from the SR or enhanced caffeine-induced tension transients with the exception that in PM, DT attenuated caffeine-induced tension transients. Thus, VP and DT have similar intracellular mechanisms of action in striated muscle. Both drugs induced calcium release from the SR and increase Ca2+ sensitivity of the contractile proteins, and thus could be the underlying mechanisms for potentiating twitch tension, and inducing contracture in skeletal muscle.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Retículo Sarcoplasmático
/
Diltiazem
/
Verapamil
/
Contração Muscular
/
Proteínas Musculares
Limite:
Animals
Idioma:
En
Revista:
Naunyn Schmiedebergs Arch Pharmacol
Ano de publicação:
1988
Tipo de documento:
Article