Changes in the mRNA Levels of Delayed Rectifier Potassium Channels in Human Atrial Fibrillation

Abstract

Introduction: We measured mRNA levels of delayed rectifier potassium channels in human atrial tissue to investigate the mechanism of the shortening of the atrial effective refractory period and the loss of rate-adaptive shortening of the atrial effective refractory period in human atrial fibrillation. Methods and Results: A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The mRNA amounts of K_VLQT1 (I_Ks), minK (β-subunit of I_Ks), HERG (I_Kr), and K_V1.5 (I_Kur) were measured by reverse transcription-polymerase chain reaction and normalized to the mRNA amount of GAPDH. We found that the mRNA levels of K_V1.5, HERG and K_VLQT1 were all significantly decreased in patients with persistent atrial fibrillation for more than 3 months. In contrast, the mRNA level of minK was significantly increased in patients with persistent atrial fibrillation for more than 3 months. We further showed that these changes were independent of the underlying cardiac disease, atrial filling pressure, gender and age. We also found that there was no spatial dispersion of mRNA levels among the four atrial sampling sites. Conclusions: Because the decrease in potassium currents results in a prolonged action potential, the shortening of the atrial effective refractory period in atrial fibrillation should be attributed to other factors. However, the decrease in I_Ks might contribute, at least in part, to the loss of rate-adaptive shortening of the atrial refractory period.