Skeletal muscle Ca2+-independent kinase activity increases during either hypertrophy or running

Departments of 1 Integrative Biology and Pharmacology and of 2 Neurobiology and Anatomy, University of Texas Medical School, Houston, Texas 77030; and 3 Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri 65211-0001 Spikes in free Ca 2+ initiate contractions in skeletal muscle cells, but whether and how they might signal to transcription factors in skeletal muscles of living animals is unknown. Since previous studies in non-muscle cells have shown that serum response factor (SRF) protein, a transcription factor, is phosphorylated rapidly by Ca 2+ /calmodulin (CaM)-dependent protein kinase after rises in intracellular Ca 2+ , we measured enzymatic activity that phosphorylates SRF (designated SRF kinase activity). Homogenates from 7-day-hypertrophied anterior latissimus dorsi muscles of roosters had more Ca 2+ -independent SRF kinase activity than their respective control muscles. However, no differences were noted in Ca 2+ /CaM-dependent SRF kinase activity between control and trained muscles. To determine whether the Ca 2+ -independent and Ca 2+ /CaM-dependent forms of Ca 2+ /CaM-dependent protein kinase II (CaMKII) might contribute to some of the SRF kinase activity, autocamtide-3, a synthetic substrate that is specific for CaMKII, was employed. While the Ca 2+ -independent form of CaMKII was increased, like the Ca 2+ -independent form of SRF kinase, no alteration in CaMKII occurred at 7 days of stretch overload. These observations suggest that some of SRF phosphorylation by skeletal muscle extracts could be due to CaMKII. To determine whether this adaptation was specific to the exercise type (i.e., hypertrophy), similar measurements were made in the white vastus lateralis muscle of rats that had completed 2 wk of voluntary running. Although Ca 2+ -independent SRF kinase was increased, no alteration occurred in Ca 2+ /CaM-dependent SRF kinase activity. Thus any role of Ca 2+ -independent SRF kinase signaling has downstream modulators specific to the exercise phenotype. exercise; adaptation; serum response factor; ionized calcium/calmodulin-dependent protein kinase II