Lee Sang Eok, Kim Dae Hoon, Son Seung Myeung, Choi Song-Yi, You Ra Young, Kim Chan Hyung, Choi Woong, Kim Hun Sik, Lim Yung Ji, Han Ji Young, Kim Hyun Woo, Yang In Jun, Xu Wen-Xie, Lee Sang Jin, Kim Young Chul, Yun Hyo-Yung
Department of Surgery, College of Medicine, Konyang University, 158 Gwanjeodong-ro, Seo-gu, Daejeon 35365, Korea.
Department of Surgery, College of Medicine, Chungbuk National University, Chungdae-ro 1, Seowon-gu, Cheongju, Chungbuk 28644, Korea.
J Smooth Muscle Res. 2020;56(0):29-45. doi: 10.1540/jsmr.56.29.
Gastric motility is controlled by slow waves. In general, the activation of the ATP-sensitive K (K) channels in the smooth muscle opposes the membrane excitability and produces relaxation. Since metabolic inhibition and/or diabetes mellitus are accompanied by dysfunctions of gastric smooth muscle, we examined the possible roles of K channels in human gastric motility. We used human gastric corpus and antrum smooth muscle preparations and recorded the mechanical activities with a conventional contractile measuring system. We also identified the subunits of the K channels using Western blot. Pinacidil (10 μM), a K channel opener, suppressed contractions to 30% (basal tone to -0.2 g) of the control. The inhibitory effect of pinacidil on contraction was reversed to 59% of the control by glibenclamide (20 μM), a K channel blocker. The relaxation by pinacidil was not affected by a pretreatment with L-arginine methyl ester, tetraethylammonium, or 4-aminopyridine. Pinacidil also inhibited the acetylcholine (ACh)-induced tonic and phasic contractions in a glibenclamide-sensitive manner (42% and 6% of the control, respectively). Other K channel openers such as diazoxide, cromakalim and nicorandil also inhibited the spontaneous and ACh-induced contractions. Calcitonin gene-related peptide (CGRP), a gastric neuropeptide, induced muscle relaxation by the activation of K channels in human gastric smooth muscle. Finally, we have found with Western blot studies, that human gastric smooth muscle expressed K channels which were composed of Kir 6.2 and SUR2B subunits.
胃动力受慢波控制。一般来说，平滑肌中ATP敏感性钾（K）通道的激活会对抗膜兴奋性并产生舒张。由于代谢抑制和/或糖尿病伴有胃平滑肌功能障碍，我们研究了钾通道在人类胃动力中的可能作用。我们使用了人胃体和胃窦平滑肌标本，并用传统的收缩测量系统记录机械活动。我们还通过蛋白质印迹法鉴定了钾通道的亚基。钾通道开放剂吡那地尔（10 μM）将收缩抑制至对照的30%（基础张力降至-0.2 g）。钾通道阻滞剂格列本脲（20 μM）可将吡那地尔对收缩的抑制作用逆转至对照的59%。吡那地尔引起的舒张不受L-精氨酸甲酯、四乙铵或4-氨基吡啶预处理的影响。吡那地尔还以格列本脲敏感的方式抑制乙酰胆碱（ACh）诱导的强直性和阶段性收缩（分别为对照的42%和6%）。其他钾通道开放剂如二氮嗪、克罗卡林和尼可地尔也抑制自发性和ACh诱导的收缩。降钙素基因相关肽（CGRP）是一种胃神经肽，通过激活人胃平滑肌中的钾通道诱导肌肉舒张。最后，我们通过蛋白质印迹研究发现，人胃平滑肌表达由Kir 6.2和SUR2B亚基组成的钾通道。
