biostudies-literatureGarg VNHLBI NIH HHS307-24https://www.ebi.ac.uk/biostudies/studies/S-EPMC3434097biostudies-literatureUnknown140(3)Ether-à-go-go (EAG) and EAG-related gene (ERG) K(+) channels are close homologues but differ markedly in their gating properties. ERG1 channels are characterized by rapid and extensive C-type inactivation, whereas mammalian EAG1 channels were previously considered noninactivating. Here, we show that human EAG1 channels exhibit an intrinsic voltage-dependent slow inactivation that is markedly enhanced in rate and extent by 1-10 µM 3-nitro-N-(4-phenoxyphenyl) benzamide, or ICA105574 (ICA). This compound was previously reported to have the opposite effect on ERG1 channels, causing an increase in current magnitude by inhibition of C-type inactivation. The voltage dependence of 2 µM ICA-induced inhibition of EAG1 current was half-maximal at -73 mV, 62 mV negative to the half-point for channel aThe Journal of general physiologyTuning of EAG K(+) channel inactivation: molecular determinants of amplification by mutations and a small molecule.PMC3434097HL55236R01 HL055236Garg VSachse FBSanguinetti MCfalseTuning of EAG K(+) channel inactivation: molecular determinants of amplification by mutations and a small molecule.Ether-à-go-go (EAG) and EAG-related gene (ERG) K(+) channels are close homologues but differ markedly in their gating properties. ERG1 channels are characterized by rapid and extensive C-type inactivation, whereas mammalian EAG1 channels were previously considered noninactivating. Here, we show that human EAG1 channels exhibit an intrinsic voltage-dependent slow inactivation that is markedly enhanced in rate and extent by 1-10 µM 3-nitro-N-(4-phenoxyphenyl) benzamide, or ICA105574 (ICA). This compound was previously reported to have the opposite effect on ERG1 channels, causing an increase in current magnitude by inhibition of C-type inactivation. The voltage dependence of 2 µM ICA-induced inhibition of EAG1 current was half-maximal at -73 mV, 62 mV negative to the half-point for channel a2012-01-01T00:00:00Z2012 Sep2026-05-03T05:19:24.245Z2019-03-27T00:57:29ZS-EPMC34340972293080310.1085/jgp.201210826