CARDIAC CALSEQUESTRIN AS A POSSIBLE TARGET FOR ARRHYTHMIA

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 seriousand asymptomatic, however, in some cases it leads to heart attack which becomes fatal. The present review focuses on stepwise understanding offunctioning 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 ECcoupling of cardiac myocyte. Any disruption in the ion flow during the EC coupling causes arrhythmia. Caions act as the trigger for the excitationcontractioncoupling,;therefore,understanding its movementis an essentialtounderstand the rhythmdisordersofthe heart.Calsequestrin (CASQ)isthe mostabundantcalciumbufferingproteinpresentin the sarcoplasmicreticulumofskeletalandcardiacmuscles. Thisreviewfurther focusesonCASQ;its structureand functions. Moreover,it describestheassociation of CASQwitharrhythmia.Withthecalcium bindingthe CASQattainsitslinearpolymericstructureon the neutralizationof itshighlyelectronegativesurface.The proteinbindscalciumwith highcapacity and intermediateaffinitywhichreleasesanduptakescalciumreversiblyduring theEC coupling.Mutation inCASQgenes hasbeenassociatedwithcatecholaminergicpolymorphicventriculartachycardia,and moreover,therearequitea fewmolecules whichareknowntobindtoCASQand bring about changesinionicbufferingproperties.Thereforeunder suitableoptimizedconditions CASQcouldbechosenas anoveltargetforcardiacarrhythmia.Scrutinizingthescopeof CASQthis reviewpresentsthe first in depth studysuggesting cardiacCASQas a possible targetforarrhythmia.2+ Keywords: Calsequestrin, Arrhythmia, Tachycardia, Bradycardia, Catecholaminergic polymorphic ventricular tachycardia, Excitation-contractioncoupling