TY - JOUR
T1 - Molecular and pharmacological properties of inwardly rectifying K+ channels of human lung cancer cells
AU - Sakai, Hideki
AU - Shimizu, Takahiro
AU - Hori, Katsuhito
AU - Ikari, Akira
AU - Asano, Shinji
AU - Takeguchi, Noriaki
N1 - Funding Information:
This work was supported in part by Grants-in-Aid from Japan Society for the Promotion of Science (to H.S. and N.T.) and the Ministry of Education, Culture, Sports, Science and Technology of Japan (to H.S. and N.T.), and by the grants from Uehara Memorial Foundation, Takeda Science Foundation, Suzuken Memorial Foundation, The Research Foundation for Pharmaceutical Sciences and Tamura Foundation for Promotion of Science and Technology (to H.S.).
PY - 2002/1/25
Y1 - 2002/1/25
N2 - 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.
AB - 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.
KW - Human
KW - K channel
KW - Multidrug resistance protein
KW - Protein kinase C
KW - Small-cell lung cancer
UR - http://www.scopus.com/inward/record.url?scp=0037169209&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(01)01567-9
DO - 10.1016/S0014-2999(01)01567-9
M3 - 学術論文
C2 - 11821018
AN - SCOPUS:0037169209
SN - 0014-2999
VL - 435
SP - 125
EP - 133
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -