Referenced in: none

Automatically associated channels: Kv2.1

Title: Changes underlying arrhythmia in the transgenic heart overexpressing Refsum disease gene-associated protein.

Authors: Jeong Tae Koh, Byung Chul Jeong, Jae Ha Kim, Young Keun Ahn, Hyang Sim Lee, Yung Hong Baik, Kyung Keun Kim

Journal, date & volume: Biochem. Biophys. Res. Commun., 2004 Jan 2 , 313, 156-62

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/14672712

Abstract
Previously, we identified a novel neuron-specific protein (PAHX-AP1) that binds to Refsum disease gene product (PAHX), and we developed transgenic (TG) mice that overexpress heart-targeted PAHX-AP1. These mice have atrial tachycardia and increased susceptibility to aconitine-induced arrhythmia. This study was undertaken to elucidate the possible changes in ion channels underlying the susceptibility to arrhythmia in these mice. RT-PCR analyses revealed that the cardiac expression of adrenergic beta(1)-receptor (ADRB1) was markedly lower, whereas voltage-gated potassium channel expression (Kv2.1) was higher in PAHX-AP1 TG mice compared with non-TG mice. However, the expression of voltage-sensitive sodium and calcium channels, and muscarinic receptor was not significantly different. Propranolol pretreatment, a non-specific beta-adrenoceptor antagonist, blocked aconitine-induced arrhythmia in non-TG mice, but not in PAHX-AP1 TG mice. Our results indicate that, in the PAHX-AP1 TG heart, the modulation of voltage-gated potassium channel and ADRB1 expression seem to be important in the electrophysiological changes associated with altered ion channel functions, but ADRB1 is not involved in the greater susceptibility to aconitine-induced arrhythmia.