Mechanism of isoproterenol-induced relaxation of the rat uterine smooth muscle: Activation of 4-aminopyridine-sensitive K+ channels

Isoproterenol에 의한 자궁근 이완의 기전 : 4-aminopyridine-sensitive K+ 채널의 개방

  • Kim, Ki-ha (College of Veterinary Medicine, Seoul National University) ;
  • Lee, Young-jae (Department Pharmacology, Korea University College of Medicine) ;
  • Cho, Myung-haing (College of Veterinary Medicine, Seoul National University) ;
  • Lee, Mun-han (College of Veterinary Medicine, Seoul National University) ;
  • Chun, Boe-gwon (Department Pharmacology, Korea University College of Medicine) ;
  • Ryu, Pan-dong (College of Veterinary Medicine, Seoul National University)
  • 김기하 (서울대학교 수의과대학) ;
  • 이영재 (고려대학교 의과대학 약리학교실) ;
  • 조명행 (서울대학교 수의과대학) ;
  • 이문한 (서울대학교 수의과대학) ;
  • 전보권 (고려대학교 의과대학 약리학교실) ;
  • 류판동 (서울대학교 수의과대학)
  • Received : 1995.10.30
  • Published : 1996.03.25

Abstract

Activation of $K^+$ channels induces relaxation of smooth muscles by reducing electrical excitability and cytosolic free $Ca^{2+}$ level. ${\beta}$-adrenergic agonist isoproterenol is known to induce relaxation of the uterine smooth muscle by membrane hyperpolarization and $K^+$ efflux. Recently it is suggested that the activity of $Ca^{2+}$-activated $K^+$ channel was increased by isoproterenol in the uterine myocytes isolated from myometrium of the pregnant rat. However, the type of $K^+$ channel mediating the relaxant effect of isopreterenol in the tissue level has not yet studied. In this work, we investigated the type of $K^+$ channels involved in the isoproterenol-induced relaxation of uterine smooth muscle by measuring the integrated insometric tension of the estrogen-treated isolated nonpregnant rat uterus. Contraction of uterine tissue was induced by oxytocin (0.2nM, 2~3 contractions/min) or high KCl(20~80mM). The result are as follows : 1. Isoproterenol($10^{-10}{\sim}10^{-4}M$) inhibited oxytocin-induced contraction of isolated rat uterus($EC_{50}=1.17{\times}10^{-10}M$). 2. Isoproterenol($10^{-10}{\sim}10^{-4}M$) effectively inhibited uterine contraction induced by low KCl(20~40mM) but little those induced by high KCl(60~80mM). 3. Relaxant effect of isoproterenol($10^{-10}{\sim}10^{-4}M$) on 0.2nM oxytocin-induced contraction was effectively reduced by 4-aminopyridine(3, 10mM) but little by TEA(10~30mM), $Ba^{2+}$($1{\sim}30{\mu}M$) and glibenclamide($100{\mu}M$). Our data suggest that the relaxant effect of isoproterenol is mediated by the $K^+$ channel(s) which can be blocked by 4-aminopyridine.