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.

Cellular electrophysiology of atrial fibrillation

“…decreased HERG expression as reported in the goat [66] and human remodeled atria [88]. Although dofetilide is highly effective in prolonging repolarization and termi-4.…”

“…Another study also reported mRNA downregulation of subunits start as early as a few hours after the onset of HERG and of KvLQT1 (KCNQ1) [88]. In the latter study atrial tachycardia.…”

“…The mRNA arrhythmia persists, more slowly-reversible and possibly expression of Kv1.5 is unchanged [13,15] or decreased even irreversible changes develop. Possible mechanisms [88], whereas protein expression, analyzed by Western-or involved in early phases of electrical remodeling include slot-blotting, is reduced in two studies [15,16]. Given the functional adaptations of ion channels, regulatory propotential importance of I / Kv1.5 as a target for atrialKur cesses and alterations in ion channel expression.…”

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

“…One may tentatively speculate that circulating anti-VGKC autoantibodies, which were present in 14% of our cohort and are known to impair K V 1 channel function, may contribute to chagasic oesophageal and heart disease by impairing K V 1.5 channel function. In support of this hypothesis is the fact that down-regulation of expression of this channel has been found to be associated with arrhythmia (Van Wagoner et al 1997;Lai et al 1999;Brundel et al 2001) which is a common feature of chagasic heart disease (Elizari 2002). Due to their function of regulating cellular excitability, impairment of K V 1.5 oesophageal smooth muscle would be expected to interfere with oesophageal contractility, and this may be relevant to the loss of normal peristalsis and failure of smooth muscle relaxation characteristic of oesophageal achalasia.…”

SNP Ser38Gly in the β-subunit of potassium channel gene KCNE1 and thyrotoxic cardiomyopathy in patients with Graves’ disease

“…Результаты многих проведенных на настоящий момент исследований свидетельствуют о том, что по-лиморфизм Ser38Gly увеличивает риск фибрилляции предсердий как в гомозиготном, так и гетерозигот-ном состоянии [21][22][23]. В нескольких исследованиях [24][25][26][27] частота аллеля 38G была значительно выше у пациентов с фибрилляцией предсердий по сравне-нию с контрольной группой: 76,4 vs 63,0%, p < 0,0024 [24]; 62,3 vs 41,8%, p = 0,009 [28]; 65,8 vs 58,2%, p = 0,005 [26].…”