The involvement of ZnT-1, a new modulator of cardiac L-type calcium channels, in [corrected] atrial tachycardia remodeling. [corrected].
Atrial fibrillation (AF), the highest occurring cardiac arrhythmia in the Western world, is associated with substantial morbidity and increased mortality. In spite of extensive research, the cause of atrial electrical remodeling, a major factor in the self-perpetuating nature of AF, is still unknown. Downregulation of L-type Ca2+ channel (LTCC) activity is the hallmark of atrial electrical remodeling. ZnT-1 is a ubiquitous membrane protein that was recently suggested to inhibit the LTCC. We have studied and shown that ZnT-1 expression inhibits LTCC function in an oocyte expression system as well as in isolated cardiomyocytes. Our data also show that rapid electrical pacing can augment ZnT-1 expression in culture as well as in the atria of rats in vivo. Finally, in a pilot study, ZnT-1 expression was found to be augmented in the atria of AF patients. These findings position ZnT-1 as a probable missing link in the mechanism underlying atrial tachycardia remodeling.
Beharier
Ofer
O
Department of Physiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Etzion
Yoram
Y
Levi
Shiri
S
Mor
Merav
M
Mor
Michal
M
Dror
Shani
S
Kahn
Joy
J
Katz
Amos
A
Moran
Arie
A
D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004562:Electrocardiography; D005786:Gene Expression Regulation; D006339:Heart Rate; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013610:Tachycardia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis
D020746:Calcium Channels, L-Type; D027682:Cation Transport Proteins; D008565:Membrane Proteins; C548550:SLC30A1 protein, Xenopus; C498299:SLC30A1 protein, human; D029867:Xenopus Proteins; C092392:Slc30a1 protein, rat