Molecular remodeling of Kv4.3 potassium channels in human atrial fibrillation.
BACKGROUND
Atrial fibrillation (AF) is associated with important alterations in cardiac ion channels that cause shortening and impaired rate adaptation of atrial repolarization. The mechanisms underlying potassium current remodeling in human AF are not clear. We investigated the effects of AF on the gene expression of the Kv4.3, Kv1.4, and Kv1.5 potassium channel subunits and correlated the findings with the transient outward (Ito) and the sustained outward (Isus or I(Kur)) potassium current.


RESULTS
Semiquantitative reverse transcription-polymerase chain reaction was used to evaluate mRNA expression, and ion currents were studied with the patch clamp technique in right atrial appendages from patients in AF and compared with those from patients in stable sinus rhythm (SR). The presence of AF was associated with a 61% reduction in Kv4.3 mRNA expression (P < 0.001 vs SR), which was paralleled by a reduction in Ito current densities in this group of patients (i.e., at +50 mV: 7.44+/-0.76 pA/pF in SR and 1.24+/-0.28 pA/pF in AF; P < 0.001 vs SR). mRNA levels of Kv1.4 were identical in the two groups. AF did not affect either the gene expression of Kv1.5 or the current densities of Isus.


CONCLUSIONS
Chronic AF in humans reduces Ito by transcriptional down-regulation of the Kv4.3 potassium channel. Altered gene expression is an important component of the electrical remodeling process and may contribute to repolarization abnormalities in AF.
Grammer
J B
JB
Department of Pharmacology, University of Tübingen, Germany. joachim.grammer@uni-tuebingen.de
Bosch
R F
RF
Kühlkamp
V
V
Seipel
L
L
D000368:Aged; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000473:pathology; D016275:Atrial Function; D015536:Down-Regulation; D004553:Electric Conductivity; D005260:Female; D006339:Heart Rate; D006801:Humans; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D051672:Shal Potassium Channels
C496977:KCNA4 protein, human; C496981:KCNA5 protein, human; C497021:KCND3 protein, human; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051672:Shal Potassium Channels; D011188:Potassium