A Single Fibre Study Of The Relationship Between Glucose Transport And Skeletal Muscle Contractility
Funder
National Health and Medical Research Council
Funding Amount
$284,625.00
Summary
Type 2 diabetes (a progressive disorder often accompanied by obesity) is claimed to be the most common metabolic disease in the world and is predicted to affect 1.15 million Australians by the year 2010. Muscle contraction (in the form of physical exercise or exercise training) is now an essential component in the management of type 2 diabetes and-or obesity.This project has been planned from a perspective that combines theoretical and experimental expertise in the field of muscle cell contracti ....Type 2 diabetes (a progressive disorder often accompanied by obesity) is claimed to be the most common metabolic disease in the world and is predicted to affect 1.15 million Australians by the year 2010. Muscle contraction (in the form of physical exercise or exercise training) is now an essential component in the management of type 2 diabetes and-or obesity.This project has been planned from a perspective that combines theoretical and experimental expertise in the field of muscle cell contractility with a keen interest in the role of skeletal muscle in glucose homeostasis. Work carried out within the scope of this project will contribute new insights into the pathogenesis of type 2 diabetes-obesity and new information on the cellular mechanisms involved in contraction-stimulated glucose transport by skeletal muscle. As part of this project we will develop single muscle cell-fibre preparations and appropriate protocols for monitoring cellular aspects of glucose transport in skeletal muscle. These preparations-protocols will have the potential to be used for testing anti-diabetic drugs directed towards intracellular targets. From an educational benefit point of view, the project will create the opportunity for 4-6 honours and 2-3 PhD students to acquire a rare and useful combination of skills and expertise in muscle cell biochemistry and physiology, while working on an issue of medical concern.Read moreRead less
Aberrant Behaviour Of Cardiac Calcium Release Channels Induced By Ryanodine Receptor Peptide Probes
Funder
National Health and Medical Research Council
Funding Amount
$315,375.00
Summary
Contraction of heart muscle is regulated by the release of calcium ions from an intracellular store known as the sarcoplasmic reticulum. Calcium is released from this store to trigger contraction and then taken up again to let the heart muscle relax. Calcium flows out from the store through a specialised type of ion channel protein known as the ryanodine receptor. Recently, genetic studies have indicted that some forms of sudden cardiac death are due to mutations in the ryanodine receptor in the ....Contraction of heart muscle is regulated by the release of calcium ions from an intracellular store known as the sarcoplasmic reticulum. Calcium is released from this store to trigger contraction and then taken up again to let the heart muscle relax. Calcium flows out from the store through a specialised type of ion channel protein known as the ryanodine receptor. Recently, genetic studies have indicted that some forms of sudden cardiac death are due to mutations in the ryanodine receptor in the heart of susceptible individuals. However, nothing is currently known about how such mutations affect the function of the ryanodine receptor or how this can cause the abnormal heart beating that leads to sudden cardiac death. This project will investigate the normal functioning of the ryanodine receptor and what aberrations occur with the different mutations. This could lead to better treatment of individuals susceptible to this type of sudden cardiac death. The effectiveness of one type of drug in preventing aberrant channel behaviour will also be examined.Read moreRead less
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