Acute Creatine Kinase Inhibition Impairs Peak Tension and Intracellular Ca2+ Release in Isolated Single Myocytes

Abstract

0598 PURPOSE: The purpose of this investigation was to study the effects of acute creatine kinase (CK) inhibition (CKi) on contractile performance and cytosolic [Ca2+] ([Ca2+]c) in single myocytes isolated from Xenopus laevis lumbrical muscle during a 2-min bout of isometric tetanic contractions (0.33 Hz frequency). METHODS: Each myocyte (n = 9) performed two identical contraction trials: control (CON) and a subsequent CKi bout. CK was inhibited with 10 μM 2,4-Dinitrofluorobenzene. [Ca2+]c was measured continuously via ratiometric fluorescence microscopy and tension by a force transducer. RESULTS: Peak tension was not significantly (p>0.05) different between CKi and CON trials during the first contraction. However, force fell significantly (P <0.05) during the 2nd contraction with CK nd i and, although there was a partial recovery toward CON values, force remained attenuated compared to CON for the remainder of the contraction bout. Initial peak [Ca2+]c following CKi was not different from CON; however, every point thereafter was significantly reduced with CKi. The reduction in peak tension seen after the first contraction was associated with a significant reduction in peak [Ca2+]c. CONCLUSIONS: These data demonstrate that initial PCr hydrolysis in single skeletal muscle fibers is crucial for maintenance of both SR Ca2+ release and peak tension during a bout of repetitive tetanic contractions. Support: NIH AR-40155, NIH 1 F32 AR-48461, Parker B. Francis foundation.