IP3 receptors contribute to muscle atrophy and maintain ribosomal RNA content during 3-day hind limb suspension in rats

Abstract

Aim: Skeletal muscle unloading leads to the upregulation of proteolytic gene expression, downregulation of protein synthesis markers, and the development of muscle atrophy. These changes are accompanied by alterations in calcium signaling. We investigated the role of Inositol 1,4,5-triphosphate (IP3) receptors (IP3Rs) in regulating calcium signaling and controlling gene expression in skeletal muscles during unloading.

Methods: Male Wistar rats were randomly assigned to 4 groups (n = 8 per group). C - vivarium control; C+2APB - vivarium control with daily intraperitoneal injections of the IP3 receptor inhibitor 2-aminoethoxydiphenyl borate (2-APB, 10 mg/ kg b.w.); HU - 3-day hind limb unloading; HU+2APB - 3-day hind limb unloading with daily 2-APB injections. After the intervention, soleus muscles were analyzed for markers of calcium metabolism and proteostasis.

Results: Three days of unloading resulted in a significant increase in nuclear phosphorylated Ca2+/calmodulin-dependent protein kinase II (p-CaMK II) content and calcineurin (CaN) expression compared to the C group (P < 0.05); this effect was prevented in the HU+2APB group. In HU+2APB rats, the decline in soleus muscle weight-to-body weight ratio was partially prevented, and the downregulation of protein synthesis markers (as seen in the HU group) was also prevented. However, proteolytic signaling markers were equally upregulated in the HU+2APB and HU groups compared to C.

Conclusion: IP3 receptor inhibition during 3-day hind limb suspension in rats partially prevented the decline in m. soleus weight index and protein synthesis markers. This effect may be attributed to alterations in the regulation of nuclear calcium signaling.

Keywords

IP3 receptors / atrophy / m. soleus / rRNA / unloading

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