Strege Peter R, Ou Yijun, Sha Lei, Rich Adam, Gibbons Simon J, Szurszewski Joseph H, Sarr Michael G, Farrugia Gianrico
Enteric Neuroscience Program, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Am J Physiol Gastrointest Liver Physiol. 2003 Dec;285(6):G1111-21. doi: 10.1152/ajpgi.00152.2003. Epub 2003 Jul 31.
Interstitial cells of Cajal (ICC) generate the electrical slow wave required for normal gastrointestinal motility. The ionic conductances expressed in human intestinal ICC are unknown. The aim of this study was to determine expression of a Na+ current in human intestinal ICC and to determine the effects of the Na+ current on the slow wave. Visually identified, freshly dissociated, single ICC were verified by the presence of c-kit mRNA by using single-cell RT-PCR. Standard whole cell currents were recorded from patch-clamped ICC held at -100 mV between pulse protocols. A Na+ current was identified in human intestinal ICC. The current activated at -55 mV and peaked at -30 mV. Extracellular N-methyl-d-glucamine abolished and QX-314 (500 microM) blocked the Na+ current, but nifedipine and Ni2+ did not. The Na+ current was activated by shear stress. Single-cell RT-PCR detected mRNA for the Na+ alpha-subunit SCN5A in single human intestinal ICC. Lidocaine (200 microm) and QX-314 (500 microM) decreased slow wave frequency, and stretch increased slow wave frequency. A mechanosensitive Na+ channel current is present in human intestinal ICC and appears to play a role in the control of intestinal motor function.
Cajal间质细胞(ICC)产生正常胃肠蠕动所需的电慢波。人类肠道ICC中表达的离子电导尚不清楚。本研究的目的是确定人类肠道ICC中Na⁺电流的表达,并确定Na⁺电流对慢波的影响。通过单细胞逆转录聚合酶链反应(RT-PCR)检测c-kit mRNA的存在,以视觉识别、新鲜解离的单个ICC进行验证。在脉冲方案之间,从钳制在-100 mV的膜片钳ICC记录标准全细胞电流。在人类肠道ICC中鉴定出一种Na⁺电流。该电流在-55 mV时激活,在-30 mV时达到峰值。细胞外N-甲基-D-葡糖胺消除该电流,QX-314(500 μM)阻断Na⁺电流,但硝苯地平和Ni²⁺无此作用。Na⁺电流由剪切应力激活。单细胞RT-PCR在单个人类肠道ICC中检测到Na⁺α亚基SCN5A的mRNA。利多卡因(200 μM)和QX-314(500 μM)降低慢波频率,拉伸增加慢波频率。人类肠道ICC中存在一种机械敏感的Na⁺通道电流,似乎在肠道运动功能控制中起作用。