Myometrial relaxation of mice via expression of two pore domain acid sensitive K<sup>+</sup>(TASK-2) channels

  • Kyu-Sang Kyeong
    Department of Obstetrics and Gynecology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
  • Seung Hwa Hong
    Department of Obstetrics and Gynecology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
  • Young Chul Kim
    Department Physiology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
  • Woong Cho
    Department of Pharmacology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
  • Sun Chul Myung
    Department of Urology, College of Medicine, Chung-Ang University, Seoul 06974, Korea.
  • Moo Yeol Lee
    Department of Physiology, College of Medicine, Chung-Ang University, Seoul 06974, Korea.
  • Ra Young You
    Department Physiology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
  • Chan Hyung Kim
    Department of Pharmacology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
  • So Yeon Kwon
    VHS Medical Center, Seoul 05368, Korea.
  • Hikaru Suzuki
    Department of Physiology, Nagoya City University Medical School, Nagoya 467-8601, Japan.
  • Yeon Jin Park
    Department of Obstetrics and Gynecology, Cheongju St. Mary's Hospital, Cheongju 28323, Korea.
  • Eun-Hwan Jeong
    Department of Obstetrics and Gynecology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
  • Hak Soon Kim
    Department of Obstetrics and Gynecology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
  • Heon Kim
    Department of Preventive Medicine, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
  • Seung Woon Lim
    Department of Obstetrics and Gynecology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
  • Wen-Xie Xu
    Department of Physiology, Shanghai Jiaotong University, School of Medicine, Shanghai, 200240, P.R. China.
  • Sang Jin Lee
    Department of Medical Education, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
  • Il Woon Ji
    Department of Obstetrics and Gynecology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.

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説明

Myometrial relaxation of mouse via expression of two-pore domain acid sensitive (TASK) channels was studied. In our previous report, we suggested that two-pore domain acid-sensing K(+) channels (TASK-2) might be one of the candidates for the regulation of uterine circular smooth muscles in mice. In this study, we tried to show the mechanisms of relaxation via TASK-2 channels in marine myometrium. Isometric contraction measurements and patch clamp technique were used to verify TASK conductance in murine myometrium. Western blot and immunehistochemical study under confocal microscopy were used to investigate molecular identity of TASK channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating outward K(+) current (NIOK) may be responsible for the quiescence of murine pregnant longitudinal myometrium. The characteristics of NIOK coincided with two-pore domain acid-sensing K(+) channels (TASK-2). NIOK in the presence of K(+) channel blockers was inhibited further by TASK inhibitors such as quinidine, bupivacaine, lidocaine, and extracellular acidosis. Furthermore, oxytocin and estrogen inhibited NIOK in pregnant myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed stronger inhibition of NIOK by quinidine and increased immunohistochemical expression of TASK-2. Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretch-activated channels in the longitudinal myometrium of mouse. Activation of TASK-2 channels seems to play an essential role for relaxing uterus during pregnancy and it might be one of the alternatives for preventing preterm delivery.

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