Fig. 1.
Concentration-dependent block of WT hERG1 and concatenated tetrameric hERG1 channels expressed in Xenopus oocytes by cisapride, dofetilide, and MK-499. (A) Concentration-effect relationship for cisapride-mediated block of concatenated WT hERG1 tetramers (WT4) and WT hERG1 channels formed naturally by coassembly of monomers (WTmonomer). The IC50 values determined by fitting data to a logistic equation (smooth curve) were 188 ± 20 nM for WT4 channels (n = 5) and 174 ± 21 nM for WTmonomer channels (n = 4). P = 0.99, two-way analysis of variance (ANOVA). (B) Concentration-effect relationship for dofetilide-mediated block of WT4 channels (IC50 = 131 ± 21 nM, n = 5) and WTmonomer channels (IC50 = 150 ± 12 nM, n = 5). P = 0.23, two-way ANOVA. (C) Concentration-effect relationship for MK-499–mediated block of WT4 channels (IC50 = 167 ± 25 nM, n = 4) and WTmonomer channels (IC50 = 64 ± 9 nM, n = 4). P < 0.0001, two-way ANOVA. For all compounds, channel inhibition was quantified by measuring currents at the end of 4-second pulses applied once every 20 seconds to a Vt of 0 mV.