%0 Journal Article %1 Xu_2005_745 %A Xu, Yanfang %A Zhang, Zhao %A Timofeyev, Valeriy %A Sharma, Dipika %A Xu, Danyan %A Tuteja, Dipika %A Dong, Pei Hong %A Ahmmed, Gias Uddin %A Ji, Yong %A Shull, Gary E %A Periasamy, Muthu %A Chiamvimonvat, Nipavan %D 2005 %J J. Physiol. %K , 15564282 ATPase, Acid Action Activation, Amino Animals, Atria, Calcium, Calcium-Activated, Cardiac, Cells, Channel Channels, Comparative Cultured, Data, Electrocardiography, Enzyme Enzymologic, Expression Extramural, Fluid, Gating, Gene Gov't, Heart Intracellular Ion Male, Mice, Molecular Muscle Myocytes, N.I.H., Non-P.H.S., Non-U.S. P.H.S., Potassium Potentials, Proteins, Recombinant Regulation, Research Sequence Sequence, Study, Support, Transgenic, U.S. Ventricles, {C}a$^{2+}$-Transporting %N Pt 3 %P 745--758 %R 10.1113/jphysiol.2004.076216 %T The effects of intracellular Ca$^2+$ on cardiac K$^+$ channel expression and activity: novel insights from genetically altered mice. %U http://dx.doi.org/10.1113/jphysiol.2004.076216 %V 562 %X We tested the hypothesis that chronic changes in intracellular Ca$^2+$ (Ca$^2+$(i)) can result in changes in ion channel expression; this represents a novel mechanism of crosstalk between changes in Ca$^2+$ cycling proteins and the cardiac action potential (AP) profile. We used a transgenic mouse with cardiac-specific overexpression of sarcoplasmic reticulum Ca$^2+$ ATPase (SERCA) isoform 1a (SERCA1a OE) with a significant alteration of SERCA protein levels without cardiac hypertrophy or failure. Here, we report significant changes in the expression of a transient outward K$^+$ current (I(to,f)), a slowly inactivating K$^+$ current (I(K,slow)) and the steady state current (I(SS)) in the transgenic mice with resultant prolongation in cardiac action potential duration (APD) compared with the wild-type littermates. In addition, there was a significant prolongation of the QT interval on surface electrocardiograms in SERCA1a OE mice. The electrophysiological changes, which correlated with changes in Ca$^2+$(i), were further corroborated by measuring the levels of ion channel protein expression. To recapitulate the in vivo experiments, the effects of changes in Ca$^2+$(i) on ion channel expression were further tested in cultured adult and neonatal mouse cardiac myocytes. We conclude that a primary defect in Ca$^2+$ handling proteins without cardiac hypertrophy or failure may produce profound changes in K$^+$ channel expression and activity as well as cardiac AP.

@article{Xu_2005_745, abstract = {We tested the hypothesis that chronic changes in intracellular {C}a$^{2+}$ ({C}a$^{2+}$(i)) can result in changes in ion channel expression; this represents a novel mechanism of crosstalk between changes in {C}a$^{2+}$ cycling proteins and the cardiac action potential (AP) profile. We used a transgenic mouse with cardiac-specific overexpression of sarcoplasmic reticulum {C}a$^{2+}$ ATPase (SERCA) isoform 1a (SERCA1a OE) with a significant alteration of SERCA protein levels without cardiac hypertrophy or failure. Here, we report significant changes in the expression of a transient outward {K}$^{+}$ current (I(to,f)), a slowly inactivating {K}$^{+}$ current (I(K,slow)) and the steady state current (I(SS)) in the transgenic mice with resultant prolongation in cardiac action potential duration (APD) compared with the wild-type littermates. In addition, there was a significant prolongation of the QT interval on surface electrocardiograms in SERCA1a OE mice. The electrophysiological changes, which correlated with changes in {C}a$^{2+}$(i), were further corroborated by measuring the levels of ion channel protein expression. To recapitulate the in vivo experiments, the effects of changes in {C}a$^{2+}$(i) on ion channel expression were further tested in cultured adult and neonatal mouse cardiac myocytes. We conclude that a primary defect in {C}a$^{2+}$ handling proteins without cardiac hypertrophy or failure may produce profound changes in {K}$^{+}$ channel expression and activity as well as cardiac AP.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Xu, Yanfang and Zhang, Zhao and Timofeyev, Valeriy and Sharma, Dipika and Xu, Danyan and Tuteja, Dipika and Dong, Pei Hong and Ahmmed, Gias Uddin and Ji, Yong and Shull, Gary E and Periasamy, Muthu and Chiamvimonvat, Nipavan}, biburl = {https://www.bibsonomy.org/bibtex/21b3f8536816c3f781568f221f6f2bc21/hake}, description = {The whole bibliography file I use.}, doi = {10.1113/jphysiol.2004.076216}, file = {Xu_2005_745.pdf:Xu_2005_745.pdf:PDF}, interhash = {f0c374e8f63f570329affc719c426381}, intrahash = {1b3f8536816c3f781568f221f6f2bc21}, journal = {J. Physiol.}, keywords = {, 15564282 ATPase, Acid Action Activation, Amino Animals, Atria, Calcium, Calcium-Activated, Cardiac, Cells, Channel Channels, Comparative Cultured, Data, Electrocardiography, Enzyme Enzymologic, Expression Extramural, Fluid, Gating, Gene Gov't, Heart Intracellular Ion Male, Mice, Molecular Muscle Myocytes, N.I.H., Non-P.H.S., Non-U.S. P.H.S., Potassium Potentials, Proteins, Recombinant Regulation, Research Sequence Sequence, Study, Support, Transgenic, U.S. Ventricles, {C}a$^{2+}$-Transporting}, month = Feb, number = {Pt 3}, pages = {745--758}, pii = {jphysiol.2004.076216}, pmid = {15564282}, timestamp = {2009-06-03T11:21:38.000+0200}, title = {The effects of intracellular {C}a$^{2+}$ on cardiac {K}$^{+}$ channel expression and activity: novel insights from genetically altered mice.}, url = {http://dx.doi.org/10.1113/jphysiol.2004.076216}, volume = 562, year = 2005 }