Biomaterial Database

Metabolic factors contributing to altered Ca2+ regulation in skeletal muscle fatigue. 2003

D S Steele, and A M Duke

School of Biomedical Sciences, University of Leeds, Leeds, UK.

OBJECTIVE Skeletal muscle fatigue is characterized by a failure to maintain force production or power output during intense exercise. Many recent studies on isolated fibres have used brief repetitive tetanic contractions to mimic fatigue resulting from intensive exercise and to investigate the underlying cellular mechanisms. Such studies have shown that characteristic changes in Ca2+ regulation occur during fatiguing stimulation. This includes prolongation of the 'Ca2+-tails' which follow each period of tetanic stimulation and a progressive rise in resting [Ca2+]. More importantly, the final stage of fatigue is associated with a rapid decrease in tetanic [Ca2+]i and force. These fatigue-induced changes in sarcoplasmic reticulum (SR) Ca2+ regulation are temporally associated with alterations in the intracellular levels of phosphate metabolites and a causal relationship has often been proposed. The aim of this review is to evaluate the evidence linking changes in the levels of phosphate metabolites and altered Ca2+ regulation during fatigue. RESULTS The following current hypotheses will be discussed: (1) the early changes in Ca2+ regulation reflect alterations in the intracellular levels of phosphate metabolites, (2) inhibition of the SR Ca2+ release mechanism (e.g. caused by ATP depletion and increased [Mg2+]) contributes to the decrease in tetanic [Ca2+]i during the final stages of fatigue and (iii) delayed entry of inorganic phosphate ions (Pi) into the SR, followed by precipitation of calcium phosphate (Ca-Pi), can explain the fatigue-induced decrease in tetanic [Ca2+]i. CONCLUSIONS There is strong evidence that changes in phosphate metabolite levels contribute to early changes in SR Ca2+ regulation during fatigue and that inhibition of the SR Ca2+ release mechanism can partially explain the rapid decrease in tetanic [Ca2+]i during the final stages of fatigue. While precipitation of Ca-Pi may occur within the SR during fatigue, there is currently insufficient evidence to establish whether this contributes to the late decline in tetanic [Ca2+]i.

UI	MeSH Term	Description	Entries
D010710	Phosphates	Inorganic salts of phosphoric acid.	Inorganic Phosphate,Phosphates, Inorganic,Inorganic Phosphates,Orthophosphate,Phosphate,Phosphate, Inorganic
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012519	Sarcoplasmic Reticulum	A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.	Reticulum, Sarcoplasmic,Reticulums, Sarcoplasmic,Sarcoplasmic Reticulums
D018482	Muscle, Skeletal	A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.	Anterior Tibial Muscle,Gastrocnemius Muscle,Muscle, Voluntary,Plantaris Muscle,Skeletal Muscle,Soleus Muscle,Muscle, Anterior Tibial,Muscle, Gastrocnemius,Muscle, Plantaris,Muscle, Soleus,Muscles, Skeletal,Muscles, Voluntary,Skeletal Muscles,Tibial Muscle, Anterior,Voluntary Muscle,Voluntary Muscles
D018763	Muscle Fatigue	A state arrived at through prolonged and strong contraction of a muscle. Studies in athletes during prolonged submaximal exercise have shown that muscle fatigue increases in almost direct proportion to the rate of muscle glycogen depletion. Muscle fatigue in short-term maximal exercise is associated with oxygen lack and an increased level of blood and muscle lactic acid, and an accompanying increase in hydrogen-ion concentration in the exercised muscle.	Fatigue, Muscle,Muscular Fatigue,Fatigue, Muscular