Activity of voltage-gated K⁺ channels is associated with cell proliferaton and Ca²⁺ influx in carcinoma cells of colon cancer

Cell proliferation of carcinoma cells DLD-1 derived from colon cancer as measured by [³H] thymidine incorporation was drastically reduced in the presence of 4-aminopyridine, an inhibitors of voltage-gated K⁺ channel. A number of nonspecific K⁺ channel inhibitors including TPeA, TEA, verapamil and diltiazem also inhibited [³H] incorporation at the concentration reported to inhibit voltage-gated K⁺ channels. The presence of voltage- gated K⁺ channels was confirmed by reverse transcription-PCR and cDNA sequencing. Charybdotoxin and iberiotoxin, inhibitors for Ca²⁺ -senstove K⁺ channel, and glibenclamide, a specific inhibitor for ATP-sensitive K⁺ channel, did not have effect on cell proliferation. These experiments suggested a critical role of voltage-gated K⁺ channels in proliferation of colon cancer cells. Mechanism of action of K⁺ channel activity in cell proliferation was explored by studying the relationship between the K⁺ channel activity and Ca²⁺ entry. The results from experiments indicated that K⁺ channel inhibitors blocked [Ca²⁺](i) influx. Therefore, it is likely that K⁺ channel activity may modulate Ca²⁺ influx into colon cancer cells, and subsequently modulate the proliferation of these cells.