How stretch activated channels contribute to muscular dystrophy
In muscular dystrophy there is increased activity of stretch-activated channels; this project aims to understand how the resulting ionic changes lead to the damage to muscles
Duchenne muscular dystrophy is severe degenerative disease of muscle which causes death in affected boys in their mid-20s. Dystrophic muscles are more sensitive to stretch-induced muscle damage and this may be part of the damage pathway. We have recently shown that blockers of stretch-activated channels prevent Na+ and Ca2+ entry into muscles following stretch-induced damage and also reduce some of the muscle damage. In this project muscles will be removed from mdx mice (an animal model of muscular dystrophy) and the ability of drugs to reduced muscle damage will be tested.
Other projects suitable for PhD students include:
- Muscle fatigue. We plan a new approach using genetically-encoded calcium indicators in a blood-perfused muscle. A multiphoton microscope will be used and the project will suit a student who likes developing new technologies.• The pacemaker region in the mouse heart contains a new discovered store-operated channel which may have a role in normal pacemaker activity. The project aims to indentify the functional role of this channel. The techniques involved include isolating intact sino-atrial nodes of mice and investigating function with electrophysiology, fluorescent calcium indicators and immunohistochemistry.
- Stretch-induced changes in cardiac muscle are involved in the Frank-Starling relation, in arrhythmogenesis and in cardiac hypertrophy. Very recent evidence suggests that the channels are encoded by TRPC1. In this project single cardiac ventricular cells will be isolated and stretched with carbon fibre rods. Using patch-clamping and confocal microscopy we will study the electrophysiological characteristics and ionic and functional consequences of the stretch-activated channels in ventricular muscle.
- The causes of the dilated cardiomyopathy which develops as an end-stage in Duchenne muscular dystrophy. Recent work has established that reactive oxygen species have a role in development of cardiomyopathy and that scavenging ROS delays the onset of heart disease. In this project we hope to identify the intracellular pathways of ROS production and the mechanisms which contribute to the development of cardiomyopathy.
Want to find out more?
Contact us to find out what’s involved in applying for a PhD.
Contact Research Expert to find out more about participating in this opportunity.
Browse for other opportunities within the Camperdown - School of Medical Sciences - Bosch Institute .
The opportunity ID for this research opportunity is: 26