A-type potassium channels in oral epithelial cells

• Main Authors: Cheng Hsiung, Chen, 陳正雄
• Other Authors: Tien-Shen Lew
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/22934741509261556296

碩士 === 國立陽明大學 === 生理學研究所 === 90 === Abstract Oral cancer, the fifth most common malignancy of the population in Taiwan and most of that are oral squamous cell carcinoma (OSCC), mainly caused by the reactive oxygen species (ROS) generated from betel chewing are increasing year by year. Evidence have shown that overexpression of an aberrant gene of N-type fast inactivation voltage-gated K channel (Kv3.4) mRNA and protein may be beneficial for the human OSCC growth without altering the cell cycle pattern of cancer cells. Whereas the results of that anti-apoptotic protein suppress Kv channels in pulmonary arterial smooth muscle cells (PASMC) have suggested that the- amplitude of whole cell current, IK, was significantly reduced and the inactivation of IK was accelerated in bcl-2 overexpressed proliferating PASMC compared with growth-arrested cells. These results suggest that inactivation of Kv channel mediated by ROS may play a vital role in OSCC cell proliferation. We, therefor, hypothesize that the inactivation of Kv3.4 is required in the process of proliferation in oral cancer cell lines under reactive oxygen species (ROS) stress. The patch clamp techniques was used on the high expression of Kv3.4 in OSCC cell line, OEC-M1. To see whether prevention of channel inactivation thus disfavor the initiation of proliferation, the effect of reducing agents, such as b-mercaptoethanol, DTT, or glutathion (GSH) on Kv3.4 has been proceeded currently. The gating kinetics of inactivation process was investigated thoroughly to characterize the role of transient outward voltage-gated Kv3.4 channels play in the OSCC. The preliminary results of our electrophysiological study, thus far, have suggested that the Kv3.4 expressed in oral cancer cell lines (OEC-M1neo) different from that of oral cancer cell lines transfected extra Kv3.4 (OEC-M1Kv3.4). Surprisingly, the chance of observing Kv3.4 channel in OSCC has apparently lower than what we have expected then. At this point, our results seems favor the hypothesis of that the inactivation of Kv3.4 is required in the process of proliferation in oral cancer cell lines under ROS stress. Whether the oncogenic potential of the Kv3.4 channels may be mediated by mobilization of the inactivation ball domain still unclear.