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Raloxifene inhibits transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes
- Source :
- European Journal of Pharmacology. 563:61-68
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
Abstract
- 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 beta-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 microM. Raloxifene at 1 microM decreased Ito1 by 40.2+/-1.9% (at +50 mV, n=14, P0.01 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 microM). Raloxifene at 1 microM decreased IKur by 57.3+/-3.3% (at +50 mV, n=10, P0.01 vs control). However, beta-estradiol inhibited Ito1 (IC50=10.3 microM) without affecting IKur. The inhibitory effects of raloxifene and beta-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.
- Subjects :
- Selective Estrogen Receptor Modulators
medicine.medical_specialty
Patch-Clamp Techniques
Potassium Channels
Time Factors
Agonist-antagonist
Action Potentials
Estrogen receptor
Pharmacology
Internal medicine
Potassium Channel Blockers
medicine
Humans
Myocyte
Myocytes, Cardiac
Raloxifene
Heart Atria
Fulvestrant
Cells, Cultured
Dose-Response Relationship, Drug
Estradiol
Atrium (architecture)
Chemistry
Estrogen Antagonists
Antagonist
Middle Aged
Antiestrogen
Endocrinology
Selective estrogen receptor modulator
Raloxifene Hydrochloride
Potassium
Delayed Rectifier Potassium Channels
medicine.drug
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 563
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....d8b8a8d2fa83e7d071ed2282b51d9180