calpastatin and Pain

Calpastatin is an endogenous inhibitor of calpain, intracellular calcium-activated protease. It has been suggested to be involved in molecular mechanisms of long-term plasticity and excitotoxic pathways. However, functions of calpastatin in vivo are still largely unknown. To examine the physiological roles of calpastatin, we subjected calpastatin-knockout mice to a comprehensive behavioral test battery.. Calpastatin-knockout mice showed decreased locomotor activity under stressful environments, and decreased acoustic startle response, but we observed no significant change in hippocampus-dependent memory function.. These results suggest that calpastatin is likely to be more closely associated with affective rather than cognitive aspects of brain function.

Topics: Animals; Anxiety; Avoidance Learning; Behavior, Animal; Calcium-Binding Proteins; Conditioning, Psychological; Exploratory Behavior; Fear; Maze Learning; Mice; Mice, Knockout; Motor Activity; Pain; Phenotype; Reflex, Startle; Rotarod Performance Test; Sensory Gating; Social Behavior; Swimming

The purpose of this study was to compare the responsiveness of changes in Ca(2+)-content and calpain-calpastatin gene expression to concentric and eccentric single-bout and repeated exercise. An exercise group (n = 14) performed two bouts of bench-stepping exercise with 8 weeks between exercise bouts, and was compared to a control-group (n = 6). Muscle strength and soreness and plasma creatine kinase and myoglobin were measured before and during 7 days following exercise bouts. Muscle biopsies were collected from m. vastus lateralis of both legs prior to and at 3, 24 h and 7 days after exercise and quantified for muscle Ca(2+)-content and mRNA levels for calpain isoforms and calpastatin. Exercise reduced muscle strength and increased muscle soreness predominantly in the eccentric leg (P < 0.05). These responses as well as plasma levels of creatine kinase and myoglobin were all attenuated after the repeated eccentric exercise bout (P < 0.05). Total muscle Ca(2+)-content did not differ between interventions. mRNA levels for calpain 2 and calpastatin were upregulated exclusively by eccentric exercise 24 h post-exercise (P < 0.05), with no alteration in expression between bouts. Calpain 1 and calpain 3 mRNA did not change at any specific time point post-exercise for either intervention. Our mRNA results suggest a regulation on the calpain-calpastatin expression response to muscle damaging eccentric exercise, but not concentric exercise. Although a repeated bout effect was demonstrated in terms of muscle function, no immediate support was provided to suggest that regulation of expression of specific system components is involved in the repeated bout adaptation.

Topics: Adaptation, Physiological; Adult; Calcium; Calcium-Binding Proteins; Calpain; Creatine Kinase; Exercise; Humans; Male; Muscle Contraction; Muscle Proteins; Muscle Strength; Myoglobin; Pain; Pain Measurement; Quadriceps Muscle; RNA, Messenger; Time Factors; Up-Regulation