TitleDifferential sensitivity of inward rectifier K+ channels to metabolic inhibitors
Publication TypeJournal Article
Year of Publication2002
AuthorsCollins, A, Larson, M
JournalJournal of Biological Chemistry
Volume277
Pagination35815-35818
Type of ArticleJournal Article
ISSN0021-9258
Abstract

Inhibition of inward rectifier K+ channels under ischemic conditions may contribute to electrophysiological consequences of ischemia such as cardiac arrhythmia. Ischemia causes metabolic inhibition, and the use of metabolic inhibitors is one experimental method of simulating ischemia. The effects of metabolic inhibitors on the activity of inward rectifier K+ channels K(ir)2.1,K(ir)2.2, and K(ir)2.3 were studied by heterologous expression in Xenopus oocytes and two-electrode voltage clamp. 10 mum carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) inhibited K(ir)2.2 and K(ir)2.3 currents but was without effect on K(ir)2.1 currents. The rate of decline of current in FCCP was faster for K(ir)2.3 than for K(ir)2.2. K(ir)2.3 was inhibited by 3 mm sodium azide (NaN4), whereas K(ir)2.1 and K(ir)2.2 were not K(ir)2.2 was inhibited by 10 mm NaN3. All three of these inward rectifiers were inhibited by lowering the pH of the solution perfusing inside-out membrane patches. K(ir)2.3 was most sensitive to pH (pK = 6.9), whereas K(ir)2.1 was least sensitive (pK = 5.9). For K(ir)2.2 the pK was 6.2. These results demonstrate the differential sensitivity of these inward rectifiers to metabolic inhibition and internal pH. The electrophysiological response of a particular cell type to ischemia may depend on the relative expression levels of different inward rectifier genes.

URL<Go to ISI>://WOS:000178275100008
DOI10.1074/jbc.M206032200