Molecular and pharmacological properties of inwardly rectifying K+ channels of human lung cancer cells.
Properties of inwardly rectifying K+ channels in small-cell lung cancer (SCLC) cells have not been clarified in detail. Here, we found inwardly rectifying K+ channels in a human SCLC cell line (RERF-LC-MA), which expresses no multidrug resistance-associated protein 1 (MRP1) and multidrug resistance P-glycoprotein (MDR1). Extracellular Ba2+ and Cs+ inhibited inwardly rectifying K+ currents of RERF-LC-MA cells in a concentration-dependent manner, but tetraethylammonium ion and glibenclamide were ineffective. Okadaic acid, an inhibitor of phosphatases 1 and 2A, and phorbol-12,13-dibutyrate, an activator of protein kinase C, significantly decreased the inwardly rectifying K+ current. Lowering the intracellular pH but not the extracellular pH decreased the K+ current. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting analysis showed that RERF-LC-MA cells express Kir2.1 mRNA and protein. The inwardly rectifying K+ current is suggested to be generated by Kir2.1 protein in the human small-cell lung cancer cell, and that the K+ channel is negatively regulated by protein kinase C and the intracellular acidic pH.
Sakai
Hideki
H
Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, 930-0194, Toyama, Japan. sakaih@ms.toyama-mpu.ac.jp
Shimizu
Takahiro
T
Hori
Katsuhito
K
Ikari
Akira
A
Asano
Shinji
S
Takeguchi
Noriaki
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology; D002712:Chlorides / Q000378:metabolism; D004594:Electrophysiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002118:Calcium; D002712:Chlorides; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011188:Potassium; D024661:Potassium Channels, Inwardly Rectifying; D011493:Protein Kinase C; D012333:RNA, Messenger; C421109:multidrug resistance-associated protein 1