Abstract
It has been shown that calpains are involved in the proteolysis of muscle proteins that occurs with eccentric contraction (ECC) and that exogenously applied nitric oxide decreases the calpain‐mediated proteolysis. The aim of this study was to examine the effects of ingestion of l‐arginine (ARG), a nitric oxide precursor, on ECC‐related calpain activation. In the first and second experiments, male Wistar rats were given ARG in water for 7 days starting from 3 days before the ECC protocol (average ingestion, ~600 mg kg‐body wt−1 day−1). Tibialis anterior muscles underwent 200 repeated ECCs and, subsequently, were excised 3 days later. Whole muscle analyses (the first experiment) revealed that ARG attenuated ECC‐induced force deficit and autolysis of calpain‐1, and increased the amounts of S‐nitrosylated calpain‐1. Regarding ryanodine receptor (RyR) and dihydropyridine receptor (DHPR), ECC‐induced proteolysis was completely inhibited by ARG, whereas the inhibition was partial for junctophilin‐1 (JP1). Skinned fiber analyses (the second experiment) showed that ARG also inhibited ECC‐elicited reductions in the ratio of depolarization‐induced to maximum Ca2+‐activated force. In the third experiment, homogenates of rested muscles were treated with S‐nitrosylating agent, S‐nitrosoglutathione (GSNO), and/or high Ca2+ concentration ([Ca2+]). Treatment with high [Ca2+] and without GSNO produced proteolysis of RyR, DHPR, and JP1. On the other hand, treatment with high [Ca2+] and GSNO caused complete inhibition of RyR and DHPR proteolysis and partial inhibition of JP1 proteolysis. These results indicate that ARG ingestion can attenuate ECC‐induced proteolysis of Ca2+ regulatory proteins and force deficit by decreasing calpain activation via S‐nitrosylation.
Highlights
Eccentric contraction (ECC) is a contraction in which skeletal muscles are stretched while contracting
Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society
We observed that immediately after ECC, force output developed by anterior (TA and extensor digitorum longus (EDL)) muscles was significantly decreased in both CON and ARG rats and there were no differences in the extent of decreases between them
Summary
Eccentric contraction (ECC) is a contraction in which skeletal muscles are stretched while contracting It is a part of normal activities such as walking downstairs or lowing a heavy weight, and is prone to result in larger and longer-lasting force deficits compared with concentric and isometric contractions (Lavender and Nosaka 2006; Kanzaki et al 2010). This is primarily because of muscle damage characterized by triad deformation (Takekura et al 2001), sarcomere inhomogeneity (Balnave et al 1997), increased membrane permeability (Lavender and Nosaka 2006), inflammation (Liao et al 2010), and proteolysis (Kanzaki et al 2010, 2014; Zhang et al 2012).
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