Transmural expression of ion channels and transporters in human nondiseased and end-stage failing hearts
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Transmural expression of ion channels and transporters in human nondiseased and end-stage failing hearts. / Soltysinska, Ewa; Olesen, Søren-Peter; Christ, Torsten; Wettwer, Erich; Varró, Andras; Grunnet, Morten; Jespersen, Thomas.
In: Pflügers Archiv: European Journal of Physiology, Vol. 459, No. 1, 2009, p. 11-23.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Transmural expression of ion channels and transporters in human nondiseased and end-stage failing hearts
AU - Soltysinska, Ewa
AU - Olesen, Søren-Peter
AU - Christ, Torsten
AU - Wettwer, Erich
AU - Varró, Andras
AU - Grunnet, Morten
AU - Jespersen, Thomas
N1 - Keywords: Action Potentials; Adolescent; Adult; Blotting, Western; Female; Gene Expression; Heart; Heart Failure; Humans; Ion Channels; Ion Transport; Male; Middle Aged; Myocardium; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction
PY - 2009
Y1 - 2009
N2 - The cardiac action potential is primarily shaped by the orchestrated function of several different types of ion channels and transporters. One of the regional differences believed to play a major role in the progression and stability of the action potential is the transmural gradient of electrical activity across the ventricular wall. An altered balance in the ionic currents across the free wall is assumed to be a substrate for arrhythmia. A large fraction of patients with heart failure experience ventricular arrhythmia. However, the underlying substrate of these functional changes is not well-established as expression analyses of human heart failure (HF) are sparse. We have investigated steady-state RNA levels by quantitative polymerase chain reaction of ion channels, transporters, connexin 43, and miR-1 in 11 end-stage HF and seven nonfailing (NF) hearts. The quantifications were performed on endo-, mid-, and epicardium of left ventricle, enabling us to establish changes in the transmural expression gradient. Transcripts encoding Cav1.2, HCN2, Kir2.1, KCNE1, SUR1, and NCX1 were upregulated in HF compared to NF while a downregulation was observed for KChIP2, SERCA2, and miR-1. Additionally, the transmural gradient of KCNE1, KChIP2, Kir6.2, SUR1, Nav1.5, NCX1, and RyR2 found in NF was only preserved for KChiP2 and Nav1.5 in HF. The transmural gradients of NCX1, Nav1.5, and KChIP2 and the downregulation of KChIP2 were confirmed by Western blotting. In conclusion, our results reveal altered expression of several cardiac ion channels and transporters which may in part explain the increased susceptibility to arrhythmia in end-state failing hearts.
AB - The cardiac action potential is primarily shaped by the orchestrated function of several different types of ion channels and transporters. One of the regional differences believed to play a major role in the progression and stability of the action potential is the transmural gradient of electrical activity across the ventricular wall. An altered balance in the ionic currents across the free wall is assumed to be a substrate for arrhythmia. A large fraction of patients with heart failure experience ventricular arrhythmia. However, the underlying substrate of these functional changes is not well-established as expression analyses of human heart failure (HF) are sparse. We have investigated steady-state RNA levels by quantitative polymerase chain reaction of ion channels, transporters, connexin 43, and miR-1 in 11 end-stage HF and seven nonfailing (NF) hearts. The quantifications were performed on endo-, mid-, and epicardium of left ventricle, enabling us to establish changes in the transmural expression gradient. Transcripts encoding Cav1.2, HCN2, Kir2.1, KCNE1, SUR1, and NCX1 were upregulated in HF compared to NF while a downregulation was observed for KChIP2, SERCA2, and miR-1. Additionally, the transmural gradient of KCNE1, KChIP2, Kir6.2, SUR1, Nav1.5, NCX1, and RyR2 found in NF was only preserved for KChiP2 and Nav1.5 in HF. The transmural gradients of NCX1, Nav1.5, and KChIP2 and the downregulation of KChIP2 were confirmed by Western blotting. In conclusion, our results reveal altered expression of several cardiac ion channels and transporters which may in part explain the increased susceptibility to arrhythmia in end-state failing hearts.
U2 - 10.1007/s00424-009-0718-3
DO - 10.1007/s00424-009-0718-3
M3 - Journal article
C2 - 19768467
VL - 459
SP - 11
EP - 23
JO - Pflügers Archiv - European Journal of Physiology
JF - Pflügers Archiv - European Journal of Physiology
SN - 0031-6768
IS - 1
ER -
ID: 18699887