Activity of voltage-gated K+ channels is associated with cell proliferation 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+-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.
Yao
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Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin. yao2068@cuhk.edu.hk
Kwan
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D015761:4-Aminopyridine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics; D020746:Calcium Channels, L-Type; D002219:Carbamates / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D018999:Charybdotoxin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating; D009532:Nickel / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D048448:Phenylcarbamates; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000145:classification / Q000235:genetics / Q000502:physiology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D019789:Tetraethylammonium / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002219:Carbamates; D010455:Peptides; D048448:Phenylcarbamates; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger; C025508:2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate; D018999:Charybdotoxin; D019789:Tetraethylammonium; C064719:iberiotoxin; D009532:Nickel; C027435:tetrapentylammonium; D015761:4-Aminopyridine; D011188:Potassium; D005905:Glyburide; D002118:Calcium