[Truncated] In this study, an investigation was undertaken into the regulation of excitation contraction coupling, calcium handling properties and SR function by protein kinase C (PKC) and phospholipase A2 (PLA2) in C2C12 myotubes, normal and mdx myotubes, and in mechanically skinned EDL muscle fibres of the rat.1. The PKC inhibitor calphostin C significantly increased the decay time of electrically induced Ca2+-dependent fluorescence changes but had no significant effect on the peak of the Ca2+-dependent fluorescence changes in C2Cl2 myotubes or the caffeine-induced Ca2+ release in skinned adult skeletal muscle fibres of the rat. The PKC activator PMA decreased the decay time of the Ca2+-dependent fluorescence changes. These results suggest that PKC is involved in the control of the SR Ca2+ pump function in skeletal muscle. Calphostin C also significantly increased the peak of the ATP-induced Ca2+ responses in C2C12 myotubes, suggesting PKC inhibition by calphostin C may modulate the phospholipase C (PLC)-inositol-(1, 4, 5) trisphosphate (IP3)-sensitive Ca2+ release. Finally, calphostin C was observed to increase the cytosolic Ca2+ concentration within 10-15 min and caused cell shrinkage and eventual necrosis.
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2002|