Effects of acute creatine kinase inhibition on metabolism and tension development in isolated single myocytes

Abstract

This study investigated the effects of acute creatine kinase (CK) inhibition (CK_i) on contractile performance, cytosolic Ca²⁺ concentration ([Ca²⁺]_c), and intracellular Po₂ (Pi ) in Xenopus laevis isolated myocytes during a 2-min bout of isometric tetanic contractions (0.33-Hz frequency). Peak tension was similar between trials during the first contraction but was significantly (P < 0.05) attenuated for all subsequent contractions in CK_i vs. control (Con). The fall in Pi (ΔPi ) from resting values was significantly greater in Con (26.0 ± 2.2 Torr) compared with CK_i (17.8 ± 1.8 Torr). However, the ratios of Con to CK_i end-peak tension (1.53 ± 0.11) and ΔPi (1.49 ± 0.11) were similar, suggesting an unaltered aerobic cost of contractions. Additionally, the mean response time (MRT) of ΔPi was significantly faster in CK_i vs. Con during both the onset (31.8 ± 5.5 vs. 49.3 ± 5.7 s; P < 0.05) and cessation (21.2 ± 4.1 vs. 68.0 ± 3.2 s; P < 0.001) of contractions. These data demonstrate that initial phosphocreatine hydrolysis in single skeletal muscle fibers is crucial for maintenance of sarcoplasmic reticulum Ca²⁺ release and peak tension during a bout of repetitive tetanic contractions. Furthermore, as Pi fell more rapidly at contraction onset in CK_i compared with Con, these data suggest that CK activity temporally buffers the initial ATP-to-ADP concentration ratio at the transition to an augmented energetic demand, thereby slowing the initial mitochondrial activation by mitigating the energetic control signal (i.e., ADP concentration, phosphorylation potential, etc.) between sites of ATP supply and demand.