title: Downregulation of voltage-gated K(+) channels in rat heart with right ventricular hypertrophy.
abstract: The effects of myocardial hypertrophy on mRNA expression levels of voltage-gated K(+) channels were investigated using monocrotaline (MCT)-induced pulmonary hypertensive rats. The ratio of right ventricle weight to left ventricle plus septum weight on day 28 was increased significantly compared with control rats [control vs. MCT: 0.27 +/- 0.01 vs. 0.58 +/- 0.03 ms (n = 8-13); P < 0.05]. Electrocardiograms showed that QRS duration [control vs. MCT: 26.4 +/- 2.6 ms vs. 31.5 +/- 5.8 ms (n = 6); P < 0.05], Q-T interval [control vs. MCT: 100.8 +/- 8.9 ms vs. 110.0 +/- 4.2 ms (n = 6); P < 0.05] and corrected Q-T interval [Q-T(c); control vs. MCT: 8.4 +/- 0. 7 ms vs. 10.2 +/- 0.4 ms (n = 6); P < 0.05] were prolonged significantly on day 28. mRNA levels of Kv1.2, 1.5, 2.1, 4.2, and 4. 3 for day 28 assessed by ribonuclease protection assays were decreased significantly from control by 60 +/- 10, 76 +/- 3, 58 +/- 5, 81 +/- 5, and 45 +/- 12%, respectively (n = 3; P < 0.005), and Kv1.4 mRNA level for day 28 was unaffected [Kv1.4, control vs. MCT: 1.0 +/- 0.28 vs. 0.88 +/- 0.44 (arbitrary units) (n = 3); not significant (NS)]. On the other hand, there was no significant difference between control and MCT rats in mRNA levels of these Kv channels for day 14 [Kv1.2 (control vs. MCT): 1.0 +/- 0.25 vs. 0.87 +/- 0.18 (n = 3), NS; Kv1.4: 1.0 +/- 0.22 vs. 1.27 +/- 0.37 (n = 3), NS; Kv1.5: 1.0 +/- 0.16 vs. 0.91 +/- 0.28 (n = 3), NS; Kv2.1: 1.0 +/- 0.26 vs. 0.99 +/- 0.25 (n = 3), NS; Kv4.2: 1.0 +/- 0.15 vs. 1.22 +/- 0.28 (n = 3), NS; Kv4.3: 1.0 +/- 0.20 vs. 1.21 +/- 0.28 (n = 3), NS]. These findings suggest that altered ventricular repolarization at the advanced stage of hypertrophy may be the result of an inhibition of gene expression of multiple types of voltage-gated K(+) channels.
authors.affiliation: Department of Circulation, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan 464-8601, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Nishiyama
authors.forename: F
authors.initials: F
authors.lastname: Kambe
authors.forename: H
authors.initials: H
authors.lastname: Seo
authors.forename: S
authors.initials: S
authors.lastname: Takeuchi
authors.forename: K
authors.initials: K
authors.lastname: Kamiya
authors.forename: I
authors.initials: I
authors.lastname: Kodama
authors.forename: J
authors.initials: J
authors.lastname: Toyama
mesh_terms: D000818:Animals; D015536:Down-Regulation; D004562:Electrocardiography; D004594:Electrophysiology; D015870:Gene Expression; D017380:Hypertrophy, Right Ventricular / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015640:Ion Channel Gating; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015221:Potassium Channels; D012333:RNA, Messenger