FUNCTIONAL-EFFECTS OF URIDINE TRIPHOSPHATE ON HUMAN SKINNED SKELETAL-MUSCLE FIBERS

Chemically skinned human skeletal muscle fibers were used to study the effects of uridine triphosphate (UTP) on the tension-pCa relationship and on Ca2+ uptake and release by the sarcoplasmic reticulum (SR). To tal replacement (2.5 mM) of adenosine triphosphate (ATP) with UTP (i) displaced the tension-pCa relationship to the left along the abcissae and increased maximum Ca2+-activated tension, both effects being large r in slow-than in fast-type fibers (ii) markedly reduced Ca2+ uptake b y the SR (evaluated by the caffeine-evoked tension) in both fiber type s; (iii) had no effect on the rate of depletion of caffeine-sensitive Ca2+ stores during soaking in relaxing solutions; (iv) induced tension in slow-but not in fast-type fibers. The effects on the SR functional properties are consistent with the notion that UTP is a poor substitu te for ATP as a substrate for the Ca ATPase pump and as an agonist of the ryanodine-sensitive Ca2+-release channel. The UTP-induced tension in human slow-type fibers is attributed to effect(s) of the nucleotide on the tension-pCa relationship of the contractile machinery. The pre sent data reveal important differences between the effects of UTP on h uman versus rat muscle fibers.