title: Cardiac hypertrophy diminished the effects of isoproterenol on delayed rectifier potassium current in rat heart.
abstract: We investigated the association between sympathetic nerve activity and delayed rectifier potassium current (I(K)) in hypertrophic rat hearts. Left ventricular hypertrophy was induced by a 50% constriction of suprarenal abdominal aorta for 6 weeks. The effects of isoproterenol on action potential duration (APD), I(K), and L-type calcium current (I(Ca)) were investigated using the whole-cell patch clamp technique. In hypertrophic rats, I(K) was decreased by 28.2%, resulting in significant APD(90) (90% repolarization) prolongation (sham: 55 +/- 3.9, hypertrophy: 98 +/- 11 ms, P = 0.01). Isoproterenol (100 nM)-stimulated I(K) was increased by 54.9% +/- 0.10% in sham-operated rats, but not in hypertrophic rats. On the other hand, isoproterenol increased I(Ca) in both sham-operated (77.7% +/- 7.6%) and hypertrophic rats (69.6% +/- 9.7%). Consequently, isoproterenol prolonged further APD in hypertrophic rats (98 +/- 11 vs. 145 +/- 8.6 ms, P < 0.01), but not in sham-operated rats (55 +/- 3.9 vs. 61 +/- 5.6 ms, n.s.). Forskolin (1 microM, an adenylyl cyclase stimulator) did not enhance I(K) in hypertrophic rats, but IBMX (100 microM, a nonselective phosphodiesterase inhibitor) enhanced the current (30.2 +/- 0.05%), as much as in sham-operated rats. We concluded that in hypertrophic hearts, I(K) was not increased by isoproterenol because of the enhanced activity of phosphodiesterase, which leads to excessive APD prolongation.
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. sakatani@koto.kpu-m.ac.jp
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sakatani
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shirayama
authors.forename: Taku
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mani
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Shiraishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsubara
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels / Q000502:physiology*; D006321:Heart / Q000294:innervation; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013566:Sympathomimetics / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D020746:Calcium Channels, L-Type; D051668:Delayed Rectifier Potassium Channels; D010726:Phosphodiesterase Inhibitors; D013566:Sympathomimetics; D005576:Colforsin; D010727:Phosphoric Diester Hydrolases; D007545:Isoproterenol; D011188:Potassium; D015056:1-Methyl-3-isobutylxanthine