Figure 4.

External K⁺ dependence of amitriptyline-induced HERG channel blockade. (Ai) Tail currents were recorded at −60 mV after a 0.5 s depolarizing pre-pulse to +20 mV from a holding potential −70 mV every 2 s at various concentrations of amitriptyline in 2 mM extracellular K⁺ concentration ([K⁺]_o). (Aii) Tail currents were recorded using the same protocol in A at various concentrations of amitriptyline in 4 mM [K⁺]_o. (B) Concentration dependence of I_HERG block by amitriptyline at different [K⁺]_o. Plot of the decrease in maximum conductance obtained from data in Ai and Aii against amitriptyline concentrations. Symbols with error bars represent mean±s.e.mean: each data obtained from five cells. Lines are the fits of data to the Hill equation, giving IC₅₀ values of 3.26±0.31, 4.78±0.37 μM and Hill coefficients of 1.17±0.13, 1.43±0.16 in 2 and 4 mM [K⁺]_o, respectively.