کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2536324 1559146 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Raloxifene inhibits transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Raloxifene inhibits transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes
چکیده انگلیسی

The selective estrogen receptor modulator raloxifene is widely used in the treatment of postmenopausal osteoporosis, and has cardioprotective properties. However, effects of raloxifene on cardiac ion channels are unclear. The present study was designed to investigate the effects of raloxifene and β-estradiol on transient outward and ultra-rapid delayed rectifier potassium currents (Ito1 and IKur) in human atrial myocytes with a whole cell patch-clamp technique. Ito1 was inhibited by raloxifene in a concentration-dependent manner with an IC50 of 0.9 μM. Raloxifene at 1 μM decreased Ito1 by 40.2 ± 1.9% (at + 50 mV, n = 14, P < 0.01 vs control). Time-dependent recovery from inactivation was slowed, and time to peak and time-dependent inactivation of Ito1 were significantly accelerated, while steady-state voltage dependent activation and inactivation of Ito1 were not affected by raloxifene. In addition, raloxifene remarkably suppressed IKur (IC50 = 0.7 μM). Raloxifene at 1 μM decreased IKur by 57.3 ± 3.3% (at + 50 mV, n = 10, P < 0.01 vs control). However, β-estradiol inhibited Ito1 (IC50 = 10.3 μM) without affecting IKur. The inhibitory effects of raloxifene and β-estradiol on Ito1 and/or IKur were unaffected by the estrogen receptor antagonist ICI 182,780. Our results indicate that raloxifene directly inhibits the human atrial repolarization potassium currents Ito1 and IKur. Whether raloxifene is beneficial for supraventricular arrhythmias remains to be studied.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 563, Issues 1–3, 1 June 2007, Pages 61–68
نویسندگان
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