Muscle Wasting

1. Cellular mechanisms underlying myogenic arteriolar tone: role of Na+/Ca2+ exchanger (NCX).
2. Prevention of Muscle Wasting in Disorders of Motor Neurones.

1.

Researcher(s):
Professor Michael Hill, Associate Dean (Research and Development), Faculty of Life Sciences, School of Medical Sciences, RMIT University.

Title:
Cellular mechanisms underlying myogenic arteriolar tone: role of Na+/Ca2+ exchanger (NCX).

Aim:
To pharmacologically demonstrate the functional significance of the NCX in arteriolar myogenic tone as well as its existence and distribution in arteriolar smooth muscle.

Summary:
Small arteries, or arterioles, are vital players in the control of blood pressure and blood flow. This level of control is mediated through their ability to change their diameter, and hence resistance, in response to signals generated within the body. Such signals include both chemical entities (for example hormones and products of metabolism) and physical factors (pressure and sheer stress).

While these responses are fundamental to the circulatory system their underlying mechanisms are not fully known. In addition to expanding basic knowledge delineation of these mechanisms may provide the identification of sites for pharmacological intervention appropriate for the targeted treatment of disorders including hypertension and diabetes mellitus.

The studies supported by the Dunlop Foundation will use sophisticated imaging techniques in combination with modern cell/molecular biology approaches to dissect out the cellular events which enable arterioles to alter their diameter in response to a changing local environment.

2.

Researcher(s):
Professor Jeffrey D. Zajac, Department of Medicine at the Austin & Repatriation Medical Centre.

Aim:
Our research is aimed at trying to understand the causes of the degenerative process with the long-term aim of developing appropriate therapies to prevent muscle wasting.

Summary:
Prevention of muscle wasting in individuals suffering from neurodegenerative disorders is a major medical problem. A group of diseases in which this is a particularly significant problem are those caused by degeneration of motor neurones. Individuals affected by conditions causing muscle wasting, particularly motor neurone diseases, suffer from weakness and inability to perform the most fundamental of functions such as speaking, eating and walking. While physical therapy plays a role in treatment, this is insufficient to prevent the underlying causes and progression of the disease. The motor neurone disease we use as a model is Kennedy’s Disease. The genetic basis of this disease is known and the function of the affected protein is well characterised. We are studying the role of this genetic mutation and the abnormal protein produced in animal models and cell culture systems with the aim of understanding the pathological mechanisms causing this form of motor neurone disease. We anticipate this will help us to understand nerve degeneration in general.