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

Kim, Ki-ha; Lee, Young-jae; Cho, Myung-haing; Lee, Mun-han; Chun, Boe-gwon; Ryu, Pan-dong

Korean Journal of Veterinary Research 1996;36(1):83-91.

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

Ki-ha Kim¹, Young-jae Lee², Myung-haing Cho¹, Mun-han Lee¹, Boe-gwon Chun², Pan-dong Ryu¹

¹College of Veterinary Medicine, Seoul National University
²Department Pharmacology, Korea University College of Medicine

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

김기하¹, 이영재², 조명행¹, 이문한¹, 전보권², 류판동¹

¹서울대학교 수의과대학
²고려대학교 의과대학 약리학교실

Abstract

Activation of $K^+$ channels induces relaxation of smooth muscles by reducing electrical excitability and cytosolic free $Ca^{2+}$ level. ${eta}$-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($EC_{50}=1.17{ imes}10^{-10}M$). 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.

Key Words: isolated uterus, oxytocin, KCl, isoproterenol, $K^+$, channel blockers