Mechanisms of the UTP-induced tension in mammalian skeletal muscles.
The mechanisms of UTP-induced tension in human and rat skinned fibers were investigated using isometric tension recordings, electrophysiological techniques and biochemical methods. In fast-type fibers from rat extensor digitorum longus (EDL) the UTP-induced tension: a) required previous loading of Ca2+ into the sarcoplasmic reticulum (SR); b) was inhibited by previous exposure to caffeine; c) was abolished by functional disruption of the SR; d) was not affected by blockade of the SR Ca(2+)-release channels by ruthenium red or heparin; e) was prevented by spermidine. These data point to the SR as the target of UTP action and suggest a pathway of UTP-induced Ca(2+)-release independent of the ryanodine- or the IP3-sensitive Ca(2+)-release channels. Accordingly, UTP failed to stimulate the electrophysiological activity of ryanodine-sensitive channels, incorporated into lipid bilayers. We suggest that UTP-induced Ca(2+)-release might occur via the channel form of the SR Ca(2+)-ATPase. The UTP-induced tension in human slow-type fibers was not affected by the SR Ca2+ content or by disruption of the SR, but was accompanied by changes in the tension-pCa relationship, namely increase in maximum Ca(2+)-activated tension, and in apparent Ca(2+)-affinity of troponin. The UTP-induced tension in slow-type fibers from rat soleus was partially inhibited by Ca(2+)-depletion from, or by disruption of the SR, and was accompanied by changes in tension/pCa relationship, similar to those observed in human fibers. Both in skinned fibers and in isolated SR vesicles, UTP was less effective than ATP as a substrate for the SR Ca(2+)-ATPase. This effect might contribute to the UTP-induced tension.
Vianna-Jorge
R
R
Departamento de Farmacologia, Universidade Federal do Rio de Janeiro, Brazil.
Mounier
Y
Y
Suarez-Kurtz
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects*; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D014544:Uridine Triphosphate / Q000494:pharmacology*
D002118:Calcium; D014544:Uridine Triphosphate