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 in vestigated underlying molecular changes by studying the relation between ge ne expression of the L-type calcium channel and potassium channels and AERP in patients with AF, Methods and Results-mRNA and protein expression were determined in the left and right atrial appendages of patients with paroxysmal (n=13) or persiste nt (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 no t in paroxysmal AF. Protein levels for the L-type Ca2+ channel and 5 potass ium channels (Kv4.3, Kv1.5, HERG, minK, and Kir3.1) were significantly redu ced in both persistent and paroxysmal AF. Furthermore, AERPs were determine d intraoperatively at 5 basic cycle lengths between 250 and 600 ms. Patient s with persistent and paroxysmal AF displayed significant shorter AERPs. Pr otein levels of all ion channels investigated correlated positively with th e AERP and with the rate adaptation of AERP, Patients with reduced ion chan nel protein expression had a shorter AERP duration and poorer rate adaptati on. Conclusions-AF is predominantly accompanied by decreased protein contents o f the L-type Ca2+ channel and several potassium channels. Reductions in L-t ype Ca2+ channel correlated with AERP and rate adaptation, and they represe nt a probable explanation for the electrophysiological changes during AF.