Effects of lomefloxacin and norfloxacin on pancreatic β-cell ATP-sensitive K+ channels

In patients administered lomefloxacin alterations in blood glucose concentrations have been observed in some cases and lomefloxacin has previously been shown to augment insulin release from rat pancreatic islets at micromolar concentrations. The aim of the present study was to compare the effects of two structurally related fluoroquinolones, lomefloxacin and norfloxacin, on ATP-sensitive K+ (K-ATP) currents from the clonal insulinoma cell line RINm5F using the whole-cell configuration of the patch-clamp technique. The application of lomefloxacin concentration-dependently blocked K-ATP currents from RINm5F cells with a half-maximally inhibitory concentration of 81 muM, whereas the application of norfloxacin (at concentrations up to 300 muM) had only minor effects on K-ATP currents. Block of pancreatic beta-cell K-ATP currents could be mediated by interaction of lomefloxacin either with the regulatory subunit (SUR1) or with the pore-forming subunit (Kir6.2). We favour the latter hypothesis, since some fluoroquinolones have recently been shown to block the pore-forming subunit of the cardiac rapid delayed rectifier K+ current I-Kr (which is encoded by HERG (human ether-a-go-go-related gene)). Thus, as demonstrated for cardiac HERG channels in previous studies and for pancreatic beta-cell K-ATP channels in the present study, fluoroquinolones differ markedly in their potencies to inhibit K+ channel activity. (C) 2003 Elsevier Science Inc. All rights reserved.