Altered Contractile Performance to Acute Creatine Kinase Inhibition in Single Myocytes is Fiber Type Dependent

Abstract

0597 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 both oxidative (O; n = 5) and glycolytic (G; n = 5) single myocytes isolated from Xenopus laevis lumbrical muscle. METHODS: Each myocyte was subjected to two identical 2-min peak tetanic contraction trials. The first trial was a control (CON) followed by a CKi bout separated with 15-min recovery. 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: As expected, peak tension in the G (compared with O) fell significantly more (P <0.05) over the course of the CON trial. In both myocyte groups, peak tension with CKi was unchanged compared to CON (P>0.05) during the initial contraction but was significantly attenuated thereafter. During the CKi treatment, in the G myocytes, peak tension fell less rapidly compared to the O fibers and continued to fall throughout the remainder of the bout. In contrast, the O fibers had a more rapid fall in peak tension (over the first 15 s) yet had a significant ‘recovery’ in peak tension over the final 30 s of the contraction trial. Peak [Ca2+]c values followed similar trends to that seen in peak tension profiles demonstrating a close coupling between SR Ca2+ release and peak tension generation. CONCLUSION: These data demonstrate that a differential reliance on initial PCr hydrolysis in single skeletal muscle fibers, which is crucial for maintenance of SR Ca2+ release and peak tension during a bout of repetitive tetanic contractions, is fiber-type dependent. Support: NIH AR-40155, NIH 1 F32 AR-48461, Parker B. Francis foundation.