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 [H-3] 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 [H-3] 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+-sensitive 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.