| Popis: |
Carnosine (β-alanyl-L-histidine), a histidine containing dipeptide, is one of the most abundant small-molecular compounds in human skeletal muscle. Supplementation with the rate limiting amino acid, β-alanine, has resulted in significant improvements to high-intensity exercise performance. The role of carnosine as an intracellular pH buffer is undisputable, yet other physiological roles have been proposed, including the potential influence of increased carnosine content on regulation of skeletal muscle calcium (Ca2+) kinetics. The movement of Ca2+ is vital during both skeletal muscle contraction and relaxation phases. The overall aim of this thesis was to investigate the effect of β-alanine supplementation on voluntary and electrically evoked contractile properties of in-vivo human skeletal muscle. To examine this research question, there were several aims of this thesis, initially to examine the effect of β-alanine supplementation on intrinsic in-vivo isometric knee extensor force production and skeletal muscle contractility in both fresh and fatigued human skeletal muscle in young (Studies 1 and 2; Chapters 4 and 5) and older (Study 3; Chapter 6) adults. The distribution of the carnosine molecule across subcellular fractions within rat skeletal muscle tissue was explored, as well as the impact of increased carnosine availability on ATPase activity, a measure associated with skeletal muscle relaxation, estimated by Pi generation. In young adults, 28-days of β-alanine supplementation did not significantly influence voluntary and evoked force responses, or the force-frequency relationship, the in-vivo analogue of the force-Ca2+ relationship, in either fresh (Studies 1 and 2; Chapters 4 and 5) or fatigued (Study 2; Chapter 5) skeletal muscle. Furthermore, older adults experiencing pre-existing declines in skeletal muscle function due to ageing, demonstrated no beneficial effect of 28-days β-alanine supplementation on voluntary or electrically evoked skeletal muscle contractions (Study 3; Chapter 6). In young adults, there was, however, a significant decline in skeletal muscle half-relaxation time (HRT) during electrically evoked octet contractions, resting and potentiated twitches (Studies 1 and 2; Chapters 4 and 5). Two possible steps influence skeletal muscle relaxation speed include the Ca2+ removal from the myoplasm and Ca2+ dissociation from troponin followed by cross-bridge detachment. Based on the in-vivo research, it was proposed that there was a direct or indirect mechanism associated with activity of the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) pump, the proposed rate-limiting step of muscle relaxation. In-vitro analysis of ATPase activity demonstrated that SERCA activity was unaffected by increased carnosine concentrations, although there was a significant increase in overall ATPase activity (Study 4; Chapter 7). The results in this thesis showed that β-alanine supplementation was effective in improving skeletal muscle HRT in young adults, although not in healthy older adults. The exact mechanism associated with the in-vivo decline in skeletal muscle HRT remains unclear, yet raising the availability of carnosine in-vitro, does increase overall ATPase activity, although not Ca2+-dependent or SERCA activity. |
