Myometrial relaxation of mice via expression of two pore domain acid sensitive K(+) (TASK-2) channels.
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.
Department of Obstetrics and Gynecology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Kyu-Sang
KS
Kyeong
Department of Obstetrics and Gynecology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Seung Hwa
SH
Hong
Department Physiology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Young Chul
YC
Kim
Department of Pharmacology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Woong
W
Cho
Department of Urology, College of Medicine, Chung-Ang University, Seoul 06974, Korea.
Sun Chul
SC
Myung
Department of Physiology, College of Medicine, Chung-Ang University, Seoul 06974, Korea.
Moo Yeol
MY
Lee
Department Physiology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Ra Young
RY
You
Department of Pharmacology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Chan Hyung
CH
Kim
VHS Medical Center, Seoul 05368, Korea.
So Yeon
SY
Kwon
Department of Physiology, Nagoya City University Medical School, Nagoya 467-8601, Japan.
Hikaru
H
Suzuki
Department of Obstetrics and Gynecology, Cheongju St. Mary's Hospital, Cheongju 28323, Korea.
Yeon Jin
YJ
Park
Department of Obstetrics and Gynecology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Eun-Hwan
EH
Jeong
Department of Obstetrics and Gynecology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Hak Soon
HS
Kim
Department of Preventive Medicine, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Heon
H
Kim
Department of Obstetrics and Gynecology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Seung Woon
SW
Lim
Department of Physiology, Shanghai Jiaotong University, School of Medicine, Shanghai, 200240, P.R. China.
Wen-Xie
WX
Xu
Department of Medical Education, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Sang Jin
SJ
Lee
Department of Obstetrics and Gynecology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Il Woon
IW
Ji
Longitudinal muscle; Myometrium; Relaxation; TASK-2