A NEW LOOK AT THE ROLE(S) OF GLYCOGEN AND SUGAR PHOSPHATES IN SKELETAL MUSCLE CONTRACTILITY
Funder
National Health and Medical Research Council
Funding Amount
$193,224.00
Summary
According to textbooks, glycogen in skeletal muscle is a homogenous molecular species whose sole role in muscle contraction is that of a carbohydrate-energy store. Likewise, sugar phosphates, such as glucose1-phosphate (G1-P), glucose 6-phosphate (G6-P), fructose 6-phosphate (F6-P) and fructose 1,6-bisphosphate (F1,6-bP) are generally presented as negatively charged compounds that act only as substrates-products of intermediary reactions in sugar degradation pathways. However, there is now compe ....According to textbooks, glycogen in skeletal muscle is a homogenous molecular species whose sole role in muscle contraction is that of a carbohydrate-energy store. Likewise, sugar phosphates, such as glucose1-phosphate (G1-P), glucose 6-phosphate (G6-P), fructose 6-phosphate (F6-P) and fructose 1,6-bisphosphate (F1,6-bP) are generally presented as negatively charged compounds that act only as substrates-products of intermediary reactions in sugar degradation pathways. However, there is now compelling evidence that (i) glycogen depletion impairs muscle contractility even when there is no shortage of cellular energy, (ii) there are two molecular forms of glycogen, and (iii) sugar phosphates can act as potent modifiers of functional domains in muscle proteins. This project addresses a number of novel questions regarding the role (s) of glycogen and sugar phosphates in muscle contractility and the cellular mechanisms involved. The knowledge produced will further our understanding of the correlation between Excitation-Contraction coupling and different intracellular glycogen pools, and of the molecular basis of prolonged effects of sugar phosphates on the contractile machinery. Furthermore, this work should also generate valuable insights into complex physiological (e.g. fatigue and aging) and pathological (e.g. atherosclerosis, metabolic myopathies) conditions which are still poorly understood.Read moreRead less
TEMPERATURE AS MODIFIER OF MAMMALIAN SKELETAL MUSCLE FUNCTION AND OF MUSCLE RESPONSIVENESS TO PHYSIOLOGICAL FACTORS
Funder
National Health and Medical Research Council
Funding Amount
$256,018.00
Summary
Contracting muscles are a major source of heat production in the body. Heat produced by contracting muscles can cause muscle damage if muscle temperature increases above 44oC. Also, overheating from external sources can cause an increase in muscle temperature in the upper physiological range of temperature (37-44oC) which can so readily happen to humans and animals caught in blistering sun or in closed cars parked in the sun. However, very little is known about what happens to the ability of the ....Contracting muscles are a major source of heat production in the body. Heat produced by contracting muscles can cause muscle damage if muscle temperature increases above 44oC. Also, overheating from external sources can cause an increase in muscle temperature in the upper physiological range of temperature (37-44oC) which can so readily happen to humans and animals caught in blistering sun or in closed cars parked in the sun. However, very little is known about what happens to the ability of the skeletal muscle to contract when the temperature increases in this upper physiological range of temperature. This project seeks to fill in this important gap in our knowledge and increase our understanding about the existence of protective mechanisms in muscle to prevent heat-induced damage to the muscle. Such mechanisms would allow the body to operate very close to the lethal range of temperature and may be mainly responsible for the severe muscle weakness in overheated individuals. Results obtained from the project can have far reaching implications for human physiology in general and muscle and exercise physiology in particular and for developing new strategies in the treatment of collapse from body overheating. The project will also produce new knowledge regarding the mechanism of action of drugs used in the treatment of certain mental disorders but which can trigger, in susceptible individuals, uncontrolled contraction of muscles and overheating.Read moreRead less