Fig. 4.
MK-499 block of concatenated hERG1 channels containing a variable number of S620T subunits. (A) Representative current traces of WT4, ST1/WT3, ST4, and STmonomer channels recorded before and after treatment of oocytes with 0.3 µM MK-499. Channels were activated with 4-second pulse to 0 mV, and tail currents were elicited at −70 mV. (B) [MK-499]–response relationships for inhibition of Itest measured at 0 mV for indicated concatenated hERG1 channels (n = 3–5). Data were fitted with a logistic equation (smooth curves). (C) IC50 values plotted as a function of the number of S620T subunits contained within a concatenated tetramer. IC50 for ST1/WT1/ST1/WT1 channels is shown as hatched bar; IC50 for STmonomer channels is shown as crosshatched bar (at far right). P < 0.0001, one-way analysis of variance; *P < 0.0001 compared with ST4 channels. (D) Plot of IC50 values versus g/gmax at 0 mV for channels as indicated by key in (B).