An intermediate-conductance Ca(2+)-activated K (+) channel mediates B lymphoma cell cycle progression induced by serum.
We have previously reported that Kv1.3 channel is expressed in Daudi cells. However, the present study demonstrates that Daudi cell cycle progression is not affected by margatoxin, a Kv1.3 channel blocker, but can be suppressed by tetraethylammonium (TEA) and 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34), a selective blocker of intermediate-conductance Ca(2+)-activated K(+) (IK) channels. Our patch-clamp data indicate that Daudi cells express an IK channel because it has a unit conductance of about 30 pS, is voltage-independent, and can be activated by submicromolar Ca(2+) and blocked by TRAM-34. Fetal bovine serum (FBS) elevated intracellular Ca(2+) concentration ([Ca(2+)](i)) and activated this IK channel. Conversely, Rituximab, a human-mouse chimeric monoclonal antibody of CD20, significantly decreased [Ca(2+)](i) and inhibited the channel. Furthermore, both FBS-induced IK channel expression and cell cycle progression were attenuated by the treatment with LY-294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. These data together suggest that a growth factor(s) in FBS triggers cell cycle progression by elevating both IK channel activity via CD20 and IK channel expression on the cell surface via PI3K. Thus, elevated IK channel activity and expression may account, in part, for Daudi cell malignant growth and proliferation.
Wang
Jing
J
Department of Medicine, University of Alabama at Birmingham, 1530 Third Avenue South, Zeigler Research Building 510, Birmingham, AL, 35294-0017, USA.
Xu
Yu-Qing
YQ
Liang
You-You
YY
Gongora
Rafael
R
Warnock
David G
DG
Ma
He-Ping
HP
D018951:Antigens, CD20 / Q000378:metabolism; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D016393:Lymphoma, B-Cell / Q000473:pathology*; D008565:Membrane Proteins / Q000096:biosynthesis; D018613:Microscopy, Confocal; D009025:Morpholines / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D044967:Serum; D019789:Tetraethylammonium / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology
D018951:Antigens, CD20; D002118:Calcium; D002867:Chromones; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011720:Pyrazoles; D019789:Tetraethylammonium; C411671:TRAM 34; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one