title: Muscle-type specific autophosphorylation of CaMKII isoforms after paced contractions.
abstract: We explored to what extent isoforms of the regulator of excitation-contraction and excitation-transcription coupling, calcium/calmodulin protein kinase II (CaMKII) contribute to the specificity of myocellular calcium sensing between muscle types and whether concentration transients in its autophosphorylation can be simulated. CaMKII autophosphorylation at Thr287 was assessed in three muscle compartments of the rat after slow or fast motor unit-type stimulation and was compared against a computational model (CaMuZclE) coupling myocellular calcium dynamics with CaMKII Thr287 phosphorylation. Qualitative differences existed between fast- (gastrocnemius medialis) and slow-type muscle (soleus) for the expression pattern of CaMKII isoforms. Phospho-Thr287 content of δA CaMKII, associated with nuclear functions, demonstrated a transient and compartment-specific increase after excitation, which contrasted to the delayed autophosphorylation of the sarcoplasmic reticulum-associated βM CaMKII. In soleus muscle, excitation-induced δA CaMKII autophosphorylation demonstrated frequency dependence (P = 0.02). In the glycolytic compartment of gastrocnemius medialis, CaMKII autophosphorylation after excitation was blunted. In silico assessment emphasized the importance of mitochondrial calcium buffer capacity for excitation-induced CaMKII autophosphorylation but did not predict its isoform specificity. The findings expose that CaMKII autophosphorylation with paced contractions is regulated in an isoform and muscle type-specific fashion and highlight properties emerging for phenotype-specific regulation of CaMKII.
authors: School of HealthCare Science, Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester M1 5GD, UK ; Laboratory for Myology, Faculty of Human Movement Sciences, MOVE Research Institute Amsterdam, VU University Amsterdam, 1081 BT Amsterdam, The Netherlands.
authors: Wouter
authors: W
authors: Eilers
authors: Department of Biomedical Engineering, Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands ; Laboratory for Muscle Plasticity, Department of Orthopedics, University of Zurich, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland.
authors: Wouter
authors: W
authors: Gevers
authors: Laboratory for Myology, Faculty of Human Movement Sciences, MOVE Research Institute Amsterdam, VU University Amsterdam, 1081 BT Amsterdam, The Netherlands.
authors: Daniëlle
authors: D
authors: van Overbeek
authors: School of HealthCare Science, Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester M1 5GD, UK ; Laboratory for Myology, Faculty of Human Movement Sciences, MOVE Research Institute Amsterdam, VU University Amsterdam, 1081 BT Amsterdam, The Netherlands.
authors: Arnold
authors: A
authors: de Haan
authors: Laboratory for Myology, Faculty of Human Movement Sciences, MOVE Research Institute Amsterdam, VU University Amsterdam, 1081 BT Amsterdam, The Netherlands.
authors: Richard T
authors: RT
authors: Jaspers
authors: Department of Biomedical Engineering, Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands.
authors: Peter A
authors: PA
authors: Hilbers
authors: Department of Biomedical Engineering, Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands.
authors: Natal
authors: N
authors: van Riel
authors: School of HealthCare Science, Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester M1 5GD, UK ; Laboratory for Muscle Plasticity, Department of Orthopedics, University of Zurich, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland.
authors: Martin
authors: M
authors: Flück
mesh_terms: D000818:Animals; D002118:Calcium / Q000737:chemistry*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000737:chemistry*; D004594:Electrophysiology; D005260:Female; D006019:Glycolysis; D007527:Isoenzymes / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry; D010641:Phenotype; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013710:Tendons / Q000473:pathology
chemical_list: D007527:Isoenzymes; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D010100:Oxygen; D002118:Calcium