Absence of calcium channel alpha1C-subunit mutation in human atrial fibrillation.
L-type voltage-gated calcium channel mutation or phenotypical variation resulting from alternative splicing has been associated with sudden arrhythmogenic death and heart failure. Changes in calcium current density, protein and mRNA expression have been associated with atrial fibrillation. We studied human atrium harvested from 16 cardiac surgery patients (coronary bypass and/or valve procedures) for mutation of Ca(v)1.2 alpha(1C) (the main pore-forming subunit of L-type voltage-gated calcium channel) for an association with atrial fibrillation. Seven patients had persistent atrial fibrillation and one was resuscitated from ventricular arrhythmia. Clinical data were collected and prospectively updated for the development of arrhythmia. Four (25%) patients had new-onset postoperative paroxysmal atrial fibrillation. DNA from all atrial specimens was amplified, extracted, and sequenced. The alpha(1C)-subunit mutation was absent in all specimens obtained from all patients, regardless of heart rhythm. This suggests that atrial fibrillation is not associated with loss-of-function mutation of the main pore-forming subunit of the L-type voltage-gated calcium channel.
Soon
Jia-Lin
JL
Department of Cardiothoracic Surgery, National Heart Center, National University of Singapore, Singapore. soon.jia.lin@nhcs.com.sg
Ping
Liao
L
Chua
Yeow-Leng
YL
Soong
Tuck-Wah
TW
Sin
Kenny Yoong-Kong
KY
D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D020746:Calcium Channels, L-Type / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006339:Heart Rate / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011446:Prospective Studies; D012846:Singapore; D013997:Time Factors; D055815:Young Adult
C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type