Figure 5.

Reduction of Kv 4.2 current by methoxamine. (A) Kv 4.2 transfected HEK cell currents at +60 mV in control (CTL), and in the presence of 50, 200 μM, and 1 mM methoxamine, as indicated. (B) dose-response relation for Kv 4.2 current block by methoxamine. Current was measured at 300 ms and data points are means±s.e.mean (n=6 at each concentration). The solid line was fit to data using equation [1]. The EC₅₀ was 363 μM with n_H=0.87, and a maximum expected block of 95%. (C) normalized mean I-V relations for Kv 4.2 current in control (n=6), 100 μM (n=5), and 500 μM (n=6) methoxamine, as indicated. Currents were normalized to control currents at +80 mV, measured at 300 ms. ^*denotes statistically significant difference from control current amplitude, P<0.05. (D) 1/τ_block values plotted vs methoxamine concentration. τ_block values were extracted as described in the Methods from fits to the rapid phase of Kv 4.2 decay in the presence of methoxamine. From equation [3a] the best least-squares fit to these data, as indicated by the solid line in Figure 7D, gave an apparent k₊₁ of 3.2×10⁴ M⁻¹ s⁻¹, and k₋₁=8.3 s⁻¹. From equation [3b], the calculated K_d was 388 μM. Data are means±s.e.mean (n=5–9 at each concentration).