title: Changes underlying arrhythmia in the transgenic heart overexpressing Refsum disease gene-associated protein.
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.
authors.affiliation: Dental Science Research Institute, Chonnam National University, Kwangju 501-190, Republic of Korea.
authors.forename: Jeong Tae
authors.initials: JT
authors.lastname: Koh
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Jeong
authors.forename: Jae Ha
authors.initials: JH
authors.lastname: Kim
authors.forename: Young Keun
authors.initials: YK
authors.lastname: Ahn
authors.forename: Hyang Sim
authors.initials: HS
authors.lastname: Lee
authors.forename: Yung Hong
authors.initials: YH
authors.lastname: Baik
authors.forename: Kyung Keun
authors.initials: KK
authors.lastname: Kim
mesh_terms: D000157:Aconitine / Q000633:toxicity; D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated / Q000096:biosynthesis*; D011433:Propranolol / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis*; D011976:Receptors, Muscarinic / Q000096:biosynthesis; D012035:Refsum Disease / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D009419:Nerve Tissue Proteins; C429045:Phyhip protein, mouse; D024642:Potassium Channels, Voltage-Gated; D018342:Receptors, Adrenergic, beta-1; D011976:Receptors, Muscarinic; D011433:Propranolol; D000157:Aconitine