C. Huchet et C. Leoty, EFFECT OF CYCLOPIAZONIC ACID ON CONTRACTILE RESPONSES IN SLOW AND FAST BUNDLES OF CREMASTER SKELETAL-MUSCLE FROM THE FERRET, Canadian journal of physiology and pharmacology, 72(8), 1994, pp. 833-840
The effects of cyclopiazonic acid (CPA) on twitch force, calcium (Ca2) uptake and release by the sarcoplasmic reticulum (SR), and Ca2+ sens
itivity of contractile apparatus were studied using intact and chemica
lly skinned cremaster fibers and compared with those on the extensor d
igitorum longus and soleus. In cremaster muscles treated with CPA (0.5
-5 mu M) a potentiation of the twitch was observed, associated with an
increase in time to peak and in time of relaxation. In Triton-skinned
fibers, CPA, at concentrations less than 10 mu M, exerted no signific
ant effect on the contractile apparatus of either slow- or fast-twitch
fibers. In slow-twitch fibers, a dose-dependent increase in Ca2+ sens
itivity was associated with a decrease in maximal tension, at CPA conc
entrations > 10 mu M. In saponin-skinned fibers, during the uptake pha
se, CPA at > 10 mu M induced a dose-dependent decrease in caffeine con
tracture. The possibility of an action on the SR Ca2+ release channel
was excluded by testing the effect of CPA during the releasing phase.
The enhancing effect of CPA (0.5-5 mu M) on mechanical activity could
be explained by an inhibition of the SR Ca2+ ATPase in skeletal muscle
cells without an effect on the contractile proteins. Our results stro
ngly suggest that CPA (< 10 mu M) has a highly specific effect on the
SR Ca2+ pump in the fast- and slow-twitch fibers and therefore could b
e a good tool to study the mechanisms of Ca2+ regulation in skeletal m
uscles. Furthermore, the study of the SR properties, using CPA, has sh
own no significant differences in the SR function of ferret cremaster
fibers in comparison with extensor digitorum longus and soleus muscles
.