CARDIAC CALSEQUESTRIN AS A POSSIBLE TARGET FOR ARRHYTHMIA
Abstract
The term arrhythmia encapsulates all the conditions which result in the change in rhythm of the heart. It is classified broadly into two classes;
tachycardia, with increased and rhythm of heart and bradycardia, with decreased rhythm of the heart. In most cases, the arrhythmias are not serious
and asymptomatic, however, in some cases it leads to heart attack which becomes fatal. The present review focuses on stepwise understanding of
functioning of the heart and its excitation-contraction (EC) coupling followed by the mechanism of arrhythmia and the present line of medications.
The systematic flow of blood in and out of the cardiac chambers is due to the rhythmic contraction and relaxation of cardiac muscle, i.e. the EC
coupling of cardiac myocyte. Any disruption in the ion flow during the EC coupling causes arrhythmia. Ca
ions act as the trigger for the excitationcontraction
coupling,;
therefore,
understanding its movement
is an essential
to
understand the rhythm
disorders
of
the heart.
Calsequestrin (CASQ)
is
the most
abundant
calcium
buffering
protein
present
in the sarcoplasmic
reticulum
of
skeletal
and
cardiac
muscles. This
review
further focuses
on
CASQ;
its structure
and functions. Moreover,
it describes
the
association of CASQ
with
arrhythmia.
With
the
calcium binding
the CASQ
attains
its
linear
polymeric
structure
on the neutralization
of its
highly
electronegative
surface.
The protein
binds
calcium
with high
capacity and intermediate
affinity
which
releases
and
uptakes
calcium
reversibly
during the
EC coupling.
Mutation in
CASQ
genes has
been
associated
with
catecholaminergic
polymorphic
ventricular
tachycardia,
and moreover,
there
are
quite
a few
molecules which
are
known
to
bind
to
CASQ
and bring about changes
in
ionic
buffering
properties.
Therefore
under suitable
optimized
conditions CASQ
could
be
chosen
as a
novel
target
for
cardiac
arrhythmia.
Scrutinizing
the
scope
of CASQ
this review
presents
the first in depth study
suggesting cardiac
CASQ
as a possible target
for
arrhythmia.
2+
Keywords: Calsequestrin, Arrhythmia, Tachycardia, Bradycardia, Catecholaminergic polymorphic ventricular tachycardia, Excitation-contraction
coupling.
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References
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