Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation.
BACKGROUND
Sustained shortening of the atrial effective refractory period (AERP), probably due to reduction in the L-type calcium current, is a major factor in the initiation and maintenance of atrial fibrillation (AF). We investigated underlying molecular changes by studying the relation between gene expression of the L-type calcium channel and potassium channels and AERP in patients with AF.


RESULTS
mRNA and protein expression were determined in the left and right atrial appendages of patients with paroxysmal (n=13) or persistent (n=16) AF and of 13 controls in sinus rhythm using reverse transcription polymerase chain reaction and slot-blot, respectively. The mRNA content of almost all investigated ion channel genes was reduced in persistent but not in paroxysmal AF. Protein levels for the L-type Ca(2+) channel and 5 potassium channels (Kv4.3, Kv1.5, HERG, minK, and Kir3.1) were significantly reduced in both persistent and paroxysmal AF. Furthermore, AERPs were determined intraoperatively at 5 basic cycle lengths between 250 and 600 ms. Patients with persistent and paroxysmal AF displayed significant shorter AERPs. Protein levels of all ion channels investigated correlated positively with the AERP and with the rate adaptation of AERP. Patients with reduced ion channel protein expression had a shorter AERP duration and poorer rate adaptation.


CONCLUSIONS
AF is predominantly accompanied by decreased protein contents of the L-type Ca(2+) channel and several potassium channels. Reductions in L-type Ca(2+) channel correlated with AERP and rate adaptation, and they represent a probable explanation for the electrophysiological changes during AF.
Brundel
B J
BJ
Department of Cardiology, Thoraxcenter University Hospital Groningen, The Netherlands. B.J.J.M.Brundel@med.rug.nl
Van Gelder
I C
IC
Henning
R H
RH
Tieleman
R G
RG
Tuinenburg
A E
AE
Wietses
M
M
Grandjean
J G
JG
Van Gilst
W H
WH
Crijns
H J
HJ
D001281:Atrial Fibrillation / Q000235:genetics* / Q000503:physiopathology; D020746:Calcium Channels, L-Type / Q000096:biosynthesis / Q000235:genetics*; D004594:Electrophysiology; D015870:Gene Expression; D006801:Humans; D007432:Intraoperative Period; D015640:Ion Channel Gating / Q000502:physiology; D008875:Middle Aged; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis
D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D012333:RNA, Messenger