Calcium signalling in the regulation of PGC-1α, PDK4 and HKII mRNA expression

The role of calcium signalling and specific intracellular calcium signalling pathways in regulating skeletal muscle tissue peroxisome proliferator-activated receptor gamma coactivator (PGC)-1 alpha, hexokinase (HK)II and pyruvate dehydrogenase kinase (PDK)4 mRNA was examined. Cultured primary rat skeletal muscle cells were incubated for 6 h in caffeine or ionomycin. Because PGC-1 alpha mRNA clearly showed greater induction with ionomycin, the latter was chosen for the main experiments, whereby cells were incubated for 6 In with either ionomycin alone or in combination with either cyclosporin A or KN-62. The PGC-1 alpha mRNA level was increased (p < 0.05) approximately six-fold and HKII mRNA content approximately two-fold by ionomycin relative to the corresponding controls, whereas the PDK4 mRNA content remained unaffected. Cyclosporin A abolished (p<0.05) and KN-62 reduced 0<0.1) the ionomycin-induced increase in PGC-1 a. mRNA. Electrical stimulation of in vitro incubated rat EDL muscle increased (p<0.05) PGC-1 alpha mRNA by 2.2-fold after 4 h of recovery relative to a resting control, and this increase was absent when muscles were incubated with KN-62 or cyclosporin A. The present data strongly suggest that calcium signalling is involved in regulating the PGC-1 alpha and HKII genes, but not PDK4. Both calcineurin and CaMK signalling seem to be involved in the calcium- and contraction- mediated PGC1 alpha up-regulation in skeletal muscle.