OUTWARD K-FIBRILLATION( CURRENT DENSITIES AND KV1.5 EXPRESSION ARE REDUCED IN CHRONIC HUMAN ATRIAL)

Chronic atrial fibrillation is associated with a shortening of the atr ial action potential duration and atrial refractory period. To test th e hypothesis that these changes are mediated by changes in the density of specific atrial K+ currents, we compared the density of K+ current s in left and right atrial myocytes and the density of delayed rectifi er K+ channel alpha-subunit proteins (Kv1.5 and Kv2.1) in left and rig ht atrial appendages from patients (n=28) in normal sinus rhythm with those from patients (n=15) in chronic atrial fibrillation (AF). Contra ry to our expectations, nystatin-perforated patch recordings of whole- cell K+ currents revealed significant reductions in both the inactivat ing (I-TO) and sustained (I-Ksus) outward K+ current densities in left and right atrial myocytes isolated from patients in chronic AF, relat ive to the I-TO and I-Ksus densities in myocytes isolated from patient s in normal sinus rhythm. Quantitative Western blot analysis revealed that although there was no change in the expression of the Kv2.1 prote in, the expression of Kv1.5 protein was reduced by >50% in both the le ft and the right atrial appendages of AF patients. The finding that Kv 1.5 expression is reduced in parallel with the reduction in delayed re ctifier K+ current density is consistent with recent suggestions that Kv1.5 underlies the major component of the delayed rectifier K+ curren t in human atrial myocytes, the ultrarapid delayed rectifier K+ curren t, I-Kur. The unexpected finding of reduced voltage-gated outward K+ c urrent densities in atrial myocytes from AF patients demonstrates the need to further examine the details of the electrophysiological remode ling that occurs during AF to enable more effective and safer therapeu tic strategies to be developed.