|
When
muscles become fatigued a number of their physiological responses
are changed; they become weaker, slower and more efficient at using
ATP to maintain tension. Our laboratory is attempting to understand
these responses with a view to eventually developing new drug
therapies that could manipulate cardiac contractility. In
particular, we would like to understand why the muscles become more
efficient as they become more fatigued.
The
ability to make muscle fibers slower and more efficient would be
very useful in treating cardiac disorders. To date, we do not
understand the molecular mechanism responsible for the increased
efficiency seen during fatigue.
Research Strategy
To
study the mechanism of fatigue, we use a preparation of
single muscle
fibers
which lack a cell membrane. These fibers are mounted on an
apparatus that can measure the mechanics of their contraction
(force, contraction velocity and stiffness). They can then be
incubated in solutions which mimic the conditions thought to occur
in muscle fibers during fatigue. In this way, we can independently
assess the effect of altering conditions, e.g., increase in H+
which may influence the response of the contractile apparatus.
Projects in Progress
Work
done in the laboratory to date has determined that an increase in
the concentration of
hydrogen ions
and/or
phosphate
affects muscle tension and contractile velocity, but we have not
played a role in fatigue. Recently we started using ADP analogs in
an effort to examine the possible role of ADP in the increased
economy oberved during fatigue. We also have improved our
tensiometer setup to be able to perform temperature jumps. |
