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(Circulation. 2000;101:2007.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Short-Term Effects of Rapid Pacing on mRNA Level of Voltage-Dependent K⁺ Channels in Rat Atrium

Electrical Remodeling in Paroxysmal Atrial Tachycardia

Takeshi Yamashita, MD; Yuji Murakawa, MD; Noriyuki Hayami, MD; Ei-ichi Fukui, MD; Yuji Kasaoka, MD; Masashi Inoue, MD; Masao Omata, MD

From the Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Correspondence to Takeshi Yamashita, MD, Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail yamt-tky{at}umin.ac.jp

Background—Atrial fibrillation causes electrophysiological changes of the atrium, thereby facilitating its maintenance. Although the expression of ion channels is modulated in chronic atrial fibrillation, it is yet unknown whether paroxysmal atrial fibrillation can also lead to electrical remodeling by affecting gene expression.

Methods and Results—To examine the short-term effects of rapid pacing on the mRNA level of voltage-dependent K⁺ channels, high-rate atrial pacing was performed in Sprague-Dawley rat hearts. Total RNA was prepared from the atrial appendages from 0 to 8 hours after the onset of pacing, and mRNA levels of Kv1.2, Kv1.4, Kv1.5, Kv2.1, Kv4.2, Kv4.3, erg, KvLQT1, and minK were determined by RNase protection assay. Among these 9 genes, the mRNA level of the Kv1.5 channel immediately and transiently increased, with bimodal peaks at 0.5 and 2 hours after the onset of pacing. Conversely, the pacing gradually and progressively decreased the mRNA levels of the Kv4.2 and Kv4.3 channels. The increase of Kv1.5 and the decrease of Kv4.2 and Kv4.3 mRNA levels were both rate dependent. In correspondence with the changes in the mRNA level, Kv1.5 channel protein transiently increased in the membrane fraction of the atrium during a 2- to 8-hour pacing period. Electrophysiological findings that the shortening of the action potential produced by 4-hour pacing was almost abolished by a low concentration of 4-aminopyridine implied that the increased Kv1.5 protein was functioning.

Conclusions—Even short-term high-rate atrial excitation could differentially alter the mRNA levels of Kv1.5, Kv4.2, and Kv4.3 in a rate-dependent manner. In particular, increased Kv1.5 gene expression, having a transient nature, implied the possible biochemical electrical remodeling unique to paroxysmal tachycardia.

Key Words: arrhythmia • fibrillation • electrophysiology • RNA

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