%0 Journal Article %1 Gyoer_2004_603 %A Gy�rke, Sandor %A Gy�rke, Inna %A Terentyev, Dmitry %A Viatchenko-Karpinski, Serge %A Williams, Simon C %D 2004 %J Biol Res %K Animals; Arrhythmias, Calcium Calcium, Calsequestrin, Cardiac, Contraction; Mutation, Myocardial Myocardium, Myocytes, Rats; Reticulum, Sarcoplasmic Signaling; chemistry/metabolism; cytology/metabolism; genetics/physiology; genetics/physiopathology; metabolism metabolism; physiology; %N 4 %P 603--607 %T Modulation of sarcoplasmic reticulum calcium release by calsequestrin in cardiac myocytes. %V 37 %X Calsequestrin (CASQ2) is a high capacity Ca-binding protein expressed inside the sarcoplasmic reticulum (SR). Mutations in the cardiac calsequestrin gene (CASQ2) have been linked to arrhythmias and sudden death induced by exercise and emotional stress. We have studied the function of CASQ2 and the consequences of arrhythmogenic CASQ2 mutations on intracellular Ca signalling using a combination of approaches of reverse genetics and cellular physiology in adult cardiac myocytes. We have found that CASQ2 is an essential determinant of the ability of the SR to store and release Ca$^2+$ in cardiac muscle. CASQ2 serves as a reservoir for Ca$^2+$ that is readily accessible for Ca$^2+$-induced Ca$^2+$ release (CICR) and also as an active Ca$^2+$ buffer that modulates the local luminal Ca-dependent closure of the SR Ca$^2+$ release channels. At the same time, CASQ2 stabilizes the CICR process by slowing the functional recharging of SR Ca$^2+$ stores. Abnormal restitution of the Ca$^2+$ release channels from a luminal Ca-dependent refractory state could account for ventricular arrhythmias associated with mutations in the CASQ2 gene.

@article{Gyoer_2004_603, abstract = {Calsequestrin (CASQ2) is a high capacity Ca-binding protein expressed inside the sarcoplasmic reticulum (SR). Mutations in the cardiac calsequestrin gene (CASQ2) have been linked to arrhythmias and sudden death induced by exercise and emotional stress. We have studied the function of CASQ2 and the consequences of arrhythmogenic CASQ2 mutations on intracellular Ca signalling using a combination of approaches of reverse genetics and cellular physiology in adult cardiac myocytes. We have found that CASQ2 is an essential determinant of the ability of the SR to store and release {C}a$^{2+}$ in cardiac muscle. CASQ2 serves as a reservoir for {C}a$^{2+}$ that is readily accessible for {C}a$^{2+}$-induced {C}a$^{2+}$ release (CICR) and also as an active {C}a$^{2+}$ buffer that modulates the local luminal Ca-dependent closure of the SR {C}a$^{2+}$ release channels. At the same time, CASQ2 stabilizes the CICR process by slowing the functional recharging of SR {C}a$^{2+}$ stores. Abnormal restitution of the {C}a$^{2+}$ release channels from a luminal Ca-dependent refractory state could account for ventricular arrhythmias associated with mutations in the CASQ2 gene.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Gy�rke, Sandor and Gy�rke, Inna and Terentyev, Dmitry and Viatchenko-Karpinski, Serge and Williams, Simon C}, biburl = {https://www.bibsonomy.org/bibtex/2ff9b135b4be8244e6e48486405551430/hake}, description = {The whole bibliography file I use.}, file = {Gyoer_2004_603.pdf:Gyoer_2004_603.pdf:PDF;Gyoer_2004_603.ps:Gyoer_2004_603.ps:PostScript}, institution = {Department of Physiology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA. sandor.gyorke@ttuhsc.edu}, interhash = {08532211f21723c4d84a6f3cede3fec0}, intrahash = {ff9b135b4be8244e6e48486405551430}, journal = {Biol Res}, keywords = {Animals; Arrhythmias, Calcium Calcium, Calsequestrin, Cardiac, Contraction; Mutation, Myocardial Myocardium, Myocytes, Rats; Reticulum, Sarcoplasmic Signaling; chemistry/metabolism; cytology/metabolism; genetics/physiology; genetics/physiopathology; metabolism metabolism; physiology;}, number = 4, pages = {603--607}, pdf = {Gyoer_2004_603.pdf}, pmid = {15709687}, timestamp = {2009-06-03T11:21:13.000+0200}, title = {Modulation of sarcoplasmic reticulum calcium release by calsequestrin in cardiac myocytes.}, volume = 37, year = 2004 }