Muscle-type specific autophosphorylation of CaMKII isoforms after paced contractions.

Wouter Eilers,Natal Van Riel,Wouter Gevers,Arnold De Haan,Daniëlle Van Overbeek,Richard T Jaspers,Peter A Hilbers,Martin Flück

doi:10.1155/2014/943806

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.

Highlights

Myocellular calcium is an important second messenger of muscle regulation
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

Summary

Introduction

Myocellular calcium is an important second messenger of muscle regulation. This role is mediated by increases in sarcoplasmic calcium concentration with functional recruitment of muscle fibers following motoneuron-induced muscle excitation (i.e., recruitment; [1]). Thereby it is observed that slow and fast contractile characteristics of motor units are reflected by differences in the (electric) firing pattern of the innervating motoneuron and concentration differences in the rise of myocellular calcium with excitation [7]. Experimental studies have established a specific preference of motoneuron activation frequencies for the three contractile types of motor units [1, 8]. Recruitment of fast-type motor units often occurs at higher stimulation frequencies [9, 10].

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Conclusion