Inhibition of hK_v7.1 current by K⁺_e. (A) Concentration-dependent inhibition of hK_v7.1 currents by K⁺_e. Cells were held at −70 mV and stepped to 40 mV to activate the current. The time course of a 30-min recording of the current magnitude as the [K⁺]_e was continuously altered as shown. The effects of K⁺_e were reversible. (B) The relationship between the relative magnitude of the hK_v7.1 current and [K⁺]_e. The relative currents were calculated by normalizing the currents at different K⁺_e to the current obtained at 4 mM K⁺_e at the test potential of 40 mV. The experimental data (□, n = 7) were at odds with the current magnitude predicted by the GHK equation (■). K_1/2 of the current inhibition of 41 ± 7 mM was obtained by fitting the data points, as shown by the blue curve using a Langmüir function as described in Materials and methods. (C) Representative current traces with varied K⁺_e. (D) Ratios of the steady state (I_steady) to the peak current (I_peak) density at the test potential of 40 mV using different K⁺_e (n = 11).