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.
%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
}