In silico study of action potential and QT interval shortening due to loss of inactivation of the cardiac rapid delayed rectifier potassium current. Export

@article{citeulike:1576686, abstract = {The rapid delayed rectifier K(+) current, I(Kr), plays a key role in repolarisation of cardiac ventricular action potentials (APs). In recent years, a novel clinical condition denoted the short QT syndrome (SQTS) has been identified and, very recently, gain in function mutations in the gene encoding the pore-forming sub-unit of the I(Kr) channel have been proposed to underlie SQTS in some patients. Here, computer simulations were used to investigate the effects of the selective loss of voltage-dependent inactivation of I(Kr) upon ventricular APs and on the QT interval of the electrocardiogram. I(Kr) and inactivation-deficient I(Kr) were incorporated into Luo-Rudy ventricular AP models. Inactivation-deficient I(Kr) produced AP shortening that was heterogeneous between endocardial, mid-myocardial, and epicardial ventricular cell models, irrespective of whether heterogeneity between these sub-regions was incorporated of slow delayed rectifier K(+) current (I(Ks)) alone, or of I(Ks) together with that of transient outward K(+) current. The selective loss of rectification of I(Kr) did not augment transmural dispersion of AP repolarisation, as AP shortening was greater in mid-myocardial than in endo- or epicardial cell models. Simulated conduction through a 1 D transmural ventricular strand was altered by incorporation of inactivation-deficient I(Kr) and the reconstructed QT interval was shortened. Collectively, these results substantiate the notion that selective loss of I(Kr) inactivation produces a gain in I(Kr) function that causes QT interval shortening.}, address = {Biological Physics Group, Physics Department, UMIST, Manchester M60 1QD, UK. h.zhang-3@umist.ac.uk}, author = {Zhang, H. and Hancox, J. C.}, citeulike-article-id = {1576686}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.bbrc.2004.07.176}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15325285}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15325285}, day = {17}, doi = {10.1016/j.bbrc.2004.07.176}, issn = {0006-291X}, journal = {Biochem Biophys Res Commun}, keywords = {1d, fibre, modelling}, month = {September}, number = {2}, pages = {693--699}, posted-at = {2007-08-20 12:06:45}, priority = {2}, title = {In silico study of action potential and QT interval shortening due to loss of inactivation of the cardiac rapid delayed rectifier potassium current.}, url = {http://dx.doi.org/10.1016/j.bbrc.2004.07.176}, volume = {322}, year = {2004} }

TY - JOUR ID - citeulike:1576686 L3 - citeulike-article-id:1576686 N2 - The rapid delayed rectifier K(+) current, I(Kr), plays a key role in repolarisation of cardiac ventricular action potentials (APs). In recent years, a novel clinical condition denoted the short QT syndrome (SQTS) has been identified and, very recently, gain in function mutations in the gene encoding the pore-forming sub-unit of the I(Kr) channel have been proposed to underlie SQTS in some patients. Here, computer simulations were used to investigate the effects of the selective loss of voltage-dependent inactivation of I(Kr) upon ventricular APs and on the QT interval of the electrocardiogram. I(Kr) and inactivation-deficient I(Kr) were incorporated into Luo-Rudy ventricular AP models. Inactivation-deficient I(Kr) produced AP shortening that was heterogeneous between endocardial, mid-myocardial, and epicardial ventricular cell models, irrespective of whether heterogeneity between these sub-regions was incorporated of slow delayed rectifier K(+) current (I(Ks)) alone, or of I(Ks) together with that of transient outward K(+) current. The selective loss of rectification of I(Kr) did not augment transmural dispersion of AP repolarisation, as AP shortening was greater in mid-myocardial than in endo- or epicardial cell models. Simulated conduction through a 1 D transmural ventricular strand was altered by incorporation of inactivation-deficient I(Kr) and the reconstructed QT interval was shortened. Collectively, these results substantiate the notion that selective loss of I(Kr) inactivation produces a gain in I(Kr) function that causes QT interval shortening. IS - 2 JF - Biochem Biophys Res Commun SN - 0006-291X AD - Biological Physics Group, Physics Department, UMIST, Manchester M60 1QD, UK. h.zhang-3@umist.ac.uk EP - 699 TI - In silico study of action potential and QT interval shortening due to loss of inactivation of the cardiac rapid delayed rectifier potassium current. VL - 322 SP - 693 KW - 1d KW - fibre KW - modelling AU - Zhang, H AU - Hancox, JC PY - 2004/09/17/ UR - http://dx.doi.org/10.1016/j.bbrc.2004.07.176 ER -