Voltage-gated K + channels support proliferation of colonic carcinoma cells Melanie Spitzner, Jiraporn Ousingsawat, Kerstin Scheidt, Karl Kunzelmann 1 ,2 and Rainer Schreiber 1 Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, Regensburg, Germany 2 Correspondence: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany. E-mail: uqkkunze@mailbox.uq.edu Plasma membrane potassium (K + ) channels are required for cell proliferation. Evidence is growing that K + channels play a central role in the development and growth of human cancer. Here we examine the contribution and the mechanism by which K + channels control proliferation of T 84 human colonic carcinoma cells. Numerous K + channels are expressed in T 84 cells, but only voltage-gated K + (Kv) channels influenced proliferation. A number of Kv channel inhibitors reduced DNA synthesis and cell number, without exerting apoptotic or toxic effects. Expression of several Kv channels, such as Eag I, Kv 3.4 and Kv 1.5, was detected in patch clamp experiments and in fluorescence-based assays using a voltage sensitive dye. The contribution of Eag I channels to proliferation was confirmed by siRNA, which abolished Eag I activity and inhibited cell growth. Inhibition of Kv channels did not interfere with the ability of T 84 cells to regulate their cell vol, but it restricted intracellular pH regulation. In addition, inhibitors of Kv channels, as well as siRNA for Eag I, attenuated intracellular Ca 2+ signaling. The data suggest that Kv channels control proliferation of colonic cancer cells by affecting intracellular pH and Ca 2+ signaling.—Spitzner, M., Ousingsawat, J., Scheidt, K., Kunzelmann, K., Schreiber, R. Voltage-gated K + channels support proliferation of colonic carcinoma cells. Key Words: Eag • T 84 • intracellular Ca 2+ • growth • Ussing chamber • patch clamp • intracellular pH • ion channels • cancer
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Voltage-gated K+ channels support proliferation of colonic carcinoma cells
Spitzner, Melanie; Ousingsawat, Jiraporn; Scheidt, Kerstin; Kunzelmann, Karl; Schreiber, Rainer
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, Volume 21 (1): 35
Fed of American Socs for Experimental Biology – Jan 1, 2007
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