EFFECTS OF URIDINE TRIPHOSPHATE ON SKINNED SKELETAL-MUSCLE FIBERS OF THE RAT

Chemically skinned muscle fibers from rat extensor digitorum longus mu scle were used to study the effects of uridine triphosphate (UTP) on C a2+ uptake and release by the sarcoplasmic reticulum (SR) and on Ca2+- activated tensions. Total replacement (2.5 mM) of adenosine triphospha te (ATP) with UTP (i) increased submaximal Ca2+-induced tension (pCa 6 .2-5.8) but diminished P-o, the maximum tension elicited by pCa 4.2, b y ca. 15%; (ii) markedly reduced Ca2+ uptake by the SR (evaluated by c affeine-elicited tension); and (iii) induced tension in Ca2+-loaded fi bers. The UTP-induced tension averaged 55% of P-o and its rates of dev elopment and decay were considerably slower than those of caffeine-evo ked tension. The UTP-induced tension (i) depended on the Ca2+-loading conditions; (ii) was reversibly blocked by brief (15 s) exposures of C a2+-loaded fibers to 5 mM EGTA or by pretreatment with caffeine; (iii) was abolished by functional disruption of the SR with the nonionic de tergent Brij-58; and (iv) persisted after blockade of the SR Ca2+ rele ase channels with ruthenium red. Exposure of Ca2+-loaded fibers to UTP depressed the tension elicited subsequently by caffeine, and enhanced the rate of depletion of caffeine-sensitive Ca2+ stores during soakin g in relaxing solutions containing 5 mM EGTA. The UTP-induced tension is attributed to increased release of Ca2+ from the SR, via a rutheniu m red insensitive pathway(s), combined with reduced Ca2+ uptake by the SR and increased Ca2+ affinity of the contractile proteins.