School of Pharmacy and Applied Science
La Trobe University, Bendigo
PO Box 199
Bendigo, Victoria 3552
AUSTRALIA
Tel: +61 3 5444 7351
Fax: +61 3 5444 7878
Email: pharmacy
@latrobe.edu.au
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Research
Cell Signals and Drug Metabolism Research Group
Research Laboratory E, Level 3, Applied Sciences 1 Building
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Michelle Gibson's
research activities are centred around studying properties of skeletal
and cardiac muscle in animal models. Some of her more recent projects
are listed below to illustrate the sort of work she is interested
in.
Physiology
and Pharmacology of Snail Heart
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The common garden snail
(Helix aspersa) has a 2 chambered heart with one auricle
and one ventricle. This is a myogenic heart, not unlike that in
the human. Yet the snail is a much more primitive animal that does
not regulate its body temperature as well as estivating (hibernating)
in harsh environmental conditions. Hence snail heart can adapt to
periods of reduced oxygen uptake by the snail as well as very cold
temperatures.
Initial studies
have shown that snail heart has some areas that are more electrically
excitable, while others require a chemical signal for activation
of contraction. There are many chemicals that have been identified
in snails that have neuroactive and cardioactive properties. My
work is involved in further characterising the properties of some
of these cardioactive compounds (ie. FMRFamide, Small CardioActive
Peptide B) in the auricle and ventricle. |
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Several project students have investigated
the effects of temperature on cardiac activation in snail heart;
how temperature alters the calcium requirements for initiation of
contraction and subsequent strength of the heart beat (and heart
rate)and basic pharmacology (dose dependence curves) for cardioactive
agents such as adrenaline, noradrenaline, acetylcholine, atropine,
dopamine, FMRFamide and Small Cardioactive Peptide B.
This year we will be investigating the
distribution of receptors for these cardioactive agents in the auricle
and ventricle of snail heart. This will involve some histochemistry,
electron microscopy and antibody binding techniques to map the different
receptor types.
Recently this work has developed into
a collaboration with David Morton and Michael Nott to investigate
the effects of iron molluscicides (such as FeEDTA)
on cardiac muscle in the snail.
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Calcium
Loading and Release Properties of Cardiac Sarcoplasmic Reticulum.
Sarcoplasmic Reticulum
(SR) in muscle tissue is modified endoplasmic reticulum (ER) that
stores and releases calcium during muscle contraction. In skeletal
muscle the SR is much more highly developed than in cardiac muscle,
but in both muscle types SR is absolutely essential for regulating
calcium movements in the myoplasm and reaching the contractile proteins
during the contraction~relaxation cycle.
Using funtionally skinned
(sarcolemma rendered leaky), the properties of calcium loading and
release by cardiac SR can be studied in very small multicellular
preparations from the right ventricle of rat heart.
While many of the properties
of SR calcium loading and release in cardiac muscle are now well
understood, we are still learning more. Recently we showed in this
laboratory that the calcium capacity of cardiac SR in functionally
skinned ventricular prepartions is very different when the muscle
is skinned in the presence of different concentrations of calcium
buffering solutions (based on the calcium chelating compound EGTA).
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These studies confirmed the contention
that the amoung of calcium that can be loaded and subsequently released
by cardiac SR depends on whether the calcium loading occurs under
"quiescent" or resting conditions, compared with "working"
or active conditions. In essence this means that the amount of calcium
stored and released by the SR varies in part depending on whether
the heart is at rest (diastolic) or working (systolic).
Many laboratories use different calcium
buffering conditions during the preration of their muscle for study,
so this information is very important to help us understand why
we may see very different results for what may be apparently the
same set of conditions.
This work has been done in collaboration
with the Muscle
Research Group, La Trobe University. |
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