Loss of Kv and MaxiK currents associated with increased MRP1 expression in small cell lung carcinoma

✍ Scribed by Hung D. Lam; Anne-Marie Lemay; Jackie Kelly; Ceredwyn E. Hill

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 253 KB
• Volume: 209
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20761

✦ Synopsis

Abstract

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 Ca^2+^‐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 Ca^2+^‐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 MaxiKα 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. J. Cell. Physiol. 209: 535–541, 2006. © 2006 Wiley‐Liss, Inc.