Loss of Kv and MaxiK currents associated with increased MRP1 expression in small cell lung carcinoma.
Regulatory volume decrease and exocrine secretion studies suggest a functional relationship between K+ and organic anion efflux. To test the hypothesis that the expression of K+ channels and MRP1 is reciprocally related, we employed the patch clamp and RT-PCR techniques on weakly (H69) and strongly MRP1-expressing (H69AR) small cell lung cancer cells. H69AR cells do not express the time- and voltage-dependent delayed rectifying K+ current (Kv) reported earlier in H69 cells and confirmed here. About 80% of the Kv current in H69 cells inactivated at 0 mV, allowing us to identify other K+ currents present in these cells. Whole-cell currents from cells dialyzed and bathed in K-gluconate as the major ions exhibited inward rectification in both cell types. Inwardly rectifying (Kir) currents in both H69 and H69AR cells showed time-dependent activation and slow inactivation at large negative potentials. H69 cells also express a threefold larger Ca2+ -stimulated K+ -selective and iberiotoxin-sensitive current relative to H69AR cells. In excised inside-out patches exposed to 145 mM symmetrical K+ solutions, H69 cells expressed a voltage- and Ca2+ -sensitive large conductance (128 +/- 5 pS) K+ channel (MaxiK). MaxiK-like currents were not observed at the whole-cell or single-channel level in H69AR cells. RT-PCR identified MaxiKalpha transcripts in H69 but not H69AR cells. These results indicate that two K+ currents (MaxiK and Kv) and the organic anion transporter MRP1 are reciprocally expressed in H69 and H69AR cells.
Lam
Hung D
HD
GI Diseases Research Unit, Hotel Dieu Hospital and Queen's University, Kingston, Ontario, Canada.
Lemay
Anne-Marie
AM
Kelly
Jackie
J
Hill
Ceredwyn E
CE
D002118:Calcium / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism*; D004553:Electric Conductivity; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002118:Calcium; D051036:Large-Conductance Calcium-Activated Potassium Channels; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010455:Peptides; D011188:Potassium; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; C064719:iberiotoxin; C421109:multidrug resistance-associated protein 1