Cardiaccalsequestrin(CASQ2)contributestointracellularCa2þ homeostasisbyvirtueofitslow- affinity/high-capacityCa2þ bindingproperties,maintainssarcoplasmicreticulum(SR)architectureand regulatesexcitation-contractioncoupling,especiallyorexclusivelyupon ?-adrenergicstimulation. Catecholaminergicpolymorphicventriculartachycardia(CPVT)isaninheritedarrhythmogenicdisease associatedwithcardiacarrestinchildrenoryoungadults.RecessiveCPVTvariantsaredueto mutationsintheCASQ2gene.Molecularandultra-structuralpropertieswerestudiedinheartsof CASQ2R33Q/R33Q and ofCASQ2/ mice frompost-natalday2toweek8.Thedrasticreductionof CASQ2-R33Qisanearlydevelopmentaleventandisaccompaniedbydown-regulationoftriadinand junctin,andmorphologicalchangesofjSRandofSR-transverse-tubulejunctions.Althoughendo- plasmic reticulumstressisactivated,nosignsofeither apoptosisorautophagyaredetected.Theother modelofrecessiveCPVT,theCASQ2/ mouse, doesnotdisplaythesameadaptivepattern. ExpressionofCASQ2-R33Qinfluences molecularandultra-structural heartdevelopment;post-natal, adaptivechangesappearcapableofensuringuntil adulthoodanewpathophysiologicalequilibrium.
Post-natal heart adaptation in a knock-in mouse model of calsequestrin 2-linked recessive catecholaminergic polymorphic ventricular tachycardia
Volpe Pompeo
2014
Abstract
Cardiaccalsequestrin(CASQ2)contributestointracellularCa2þ homeostasisbyvirtueofitslow- affinity/high-capacityCa2þ bindingproperties,maintainssarcoplasmicreticulum(SR)architectureand regulatesexcitation-contractioncoupling,especiallyorexclusivelyupon ?-adrenergicstimulation. Catecholaminergicpolymorphicventriculartachycardia(CPVT)isaninheritedarrhythmogenicdisease associatedwithcardiacarrestinchildrenoryoungadults.RecessiveCPVTvariantsaredueto mutationsintheCASQ2gene.Molecularandultra-structuralpropertieswerestudiedinheartsof CASQ2R33Q/R33Q and ofCASQ2/ mice frompost-natalday2toweek8.Thedrasticreductionof CASQ2-R33Qisanearlydevelopmentaleventandisaccompaniedbydown-regulationoftriadinand junctin,andmorphologicalchangesofjSRandofSR-transverse-tubulejunctions.Althoughendo- plasmic reticulumstressisactivated,nosignsofeither apoptosisorautophagyaredetected.Theother modelofrecessiveCPVT,theCASQ2/ mouse, doesnotdisplaythesameadaptivepattern. ExpressionofCASQ2-R33Qinfluences molecularandultra-structural heartdevelopment;post-natal, adaptivechangesappearcapableofensuringuntil adulthoodanewpathophysiologicalequilibrium.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
