FIGURE 1.

Desipramine reduces hERG surface expression on short term exposure. A, Western blot shows time-dependent effects of incubation with 30 μm desipramine (desip.) on hERG protein stably expressed in HEK293 cells. Equal amounts of protein were loaded; fg indicates glycosylated, 150-kDa cell surface form of hERG; cg indicates core-glycosylated, 135-kDa ER-resident form of hERG. B, quantitative analysis of time-dependent changes in fg- and cg-hERG levels after exposure to 30 μm desipramine is shown. Effects of 0 K⁺ on fg-hERG are included for comparison. Image densities on Western blots were normalized to fg-hERG levels measured at t = 0. Note that cg-hERG is increased at t = 16 h (n = 3–4). C, shown are representative hERG current families recorded under control conditions or after a 6-h exposure to 30 μm desipramine. Currents were elicited using depolarizing voltage steps from −60 to +60 mV. Tail currents were recorded on return to −50 mV. Holding potential was −80 mV. D, time-dependent reduction of hERG tail current densities on exposure to 30 μm desipramine (n = 6–17) is shown. Data are given as the mean ± S.E.