Contractile Proteins
Related posters from Biophysics 2003
See also our collaborator's pages
Recent human studies show that non-infarcted zones of the left ventricle
(even those remote from the ischemic region) suffer from contractile dysfunction
early after myocardial infarction (MI). This remote-zone left-ventricular
dysfunction (RZLVD) may contribute to the high incidence of pump failure
after large MI. As the molecular basis for RZLVD remains the subject of
debate, we tested the hypothesis that the contractile apparatus itself
is directly affected in early RZLVD. 
Mouse
hearts (n=6) were infarcted in vivo with 1 hr of coronary occlusion followed
by 24 hr of reperfusion. . Cardiac myosin and native thin filaments were
purified from tissue samples taken from both the non-necrotic zone adjacent
to the infarct, and the non-ischemic zone remote from the infarct. Filament
velocities measured by in vitro motility were significantly reduced in
samples from both the adjacent (42±6% of control) and remote (72±5%
of control) zones when compared to control proteins (p<0.05). At saturating
calcium, thin filament velocities over control myosin where unaffected.
In contrast, the velocities of control thin filaments over experimental
myosin reflected the regional reductions in velocity noted above. These
data suggest that RZLVD results from an acute dysfunction of myosin.
Reactive oxygen and nitrogen species have been implicated in the pathophysiology
of both the acute and chronic phases of left ventricular dysfunction (LVD)
following large MI. A leading hypothesis is that reactive nitrogen species,
including nitric oxide (NO·) and peroxynitrite (ONOO-), covalently
modify proteins and alter the calcium sensitivity of the contractile apparatus.
We tested the hypothesis that ONOO- alters the calcium regulation of thin
filaments in the in vitro motility assay. Cardiac thin filaments and myosin
were isolated from rat hearts, and the thinfilaments 
exposedto
1 and 10 uM ONOO-. Thin filament velocities were significantly reduced,
but the [Ca] necessary for half-maximal activation remained constant at
both concentrations, within experimental error. These data bring into
question the hypothesis that reactive nitrogen species alter the calcium
sensitivity of thin filaments.
