It is well established that K⁺ channels play a role in cell proliferation and cancer development. We investigated the impact of K⁺ channels in cell proliferation of the human colonic epithelial cell line T84. Proliferation assays showed that blocking of voltage gated K⁺ (Kv) and EAG1 channels by TPeA, 4-AP, astemizole and terfenadine led to reduction of cell proliferation. Results of patch clamp experiments indicated that proliferation of T84 cells depended on the hyperpolarizing activity of Kv- and EAG1 channels. Additionally, a cell cycle dependent change of EAG channel activity could be demonstrated. In the presence of Kv and EAG channel blockers 4-AP and astemizole, the carbachol induced increase in the intracellular calcium concentration and the activity of the Na⁺/H⁺ exchanger was significantly reduced. These results indicate that Kv and EAG channels modulate intracellular Ca²⁺ and pH signalling, which are important determinants for cell cycle regulation and cell proliferation.

Supported by DFG SCHR 752/2-1 and SCHR 752/2-2 and Wilhelm Sander Stiftung 2005.063.1