Cardiac hypertrophy diminished the effects of isoproterenol on delayed rectifier potassium current in rat heart.
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.
Sakatani
Tomohiko
T
Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. sakatani@koto.kpu-m.ac.jp
Shirayama
Takeshi
T
Yamamoto
Taku
T
Mani
Hiroki
H
Shiraishi
Hirokazu
H
Matsubara
Hiroaki
H
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*
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