Alterations in potassium channel gene expression in atria of patients withpersistent and paroxysmal atrial fibrillation: Differential regulation of protein and mRNA levels for K+ channels

OBJECTIVES Our purpose was to determine whether patients with persistent at rial fibrillation (AF) and patients with paroxysmal AF show alterations in potassium channel expression. BACKGROUND Persistent AF is associated with a sustained shortening of the a trial action potential duration and atrial refractory period. Underlying mo lecular changes have not been studied in humans. We, investigated whether a changed gene expression of specific potassium channels is associated with these changes in patients with persistent AF and in patients with paroxysma l AF. METHODS Right atrial appendages were obtained from 8 patients with paroxysm al AF, 10 with persistent AF and 18 matched controls in sinus rhythm. All c ontrols underwent coronary artery bypass surgery, whereas most AF patients underwent Cox's MAZE surgery (atrial arrhythmia surgery to cure AF) (n = 12 ). All patients had normal left ventricular function. mRNA (ribonucleic aci d) levels were measured by semiquantitative polymerase chain reaction and p rotein content by Western blotting. RESULTS mRNA levels of transient outward channel (Kv4.3), acetylcholine-dep endent potassium channel (Kir3.4) and ATP-dependent potassium channel (Kir6 .2) were reduced in patients with persistent AF (-35%, -47%, and -36%, resp ectively, p < 0.05), whereas only Kv4.3 mRNA level was reduced in patients with paroxysmal AF (-29%, p = 0.03). No changes were found for Kv1.5 and HE RG mRNA levels in either group. Protein levels of Kv4.3, Kv1.5 and Kir3.1 w ere reduced both in patients with persistent AF (-39%, -84% and -47%, respe ctively, p < 0.05) and in those with paroxysmal AF (-57%, -64%, and -40%, r espectively, p < 0.05). CONCLUSIONS Persistent AF is accompanied by reductions in mRNA and protein levels of several potassium channels. In patients with paroxysmal AF these reductions were observed predominantly at the protein level and not at the mRNA level, suggesting a post-transcriptional regulation. (J Am Coil Cardio l 2001;37:926-32) (C) 2001 by the American College of Cardiology.