Voltage-dependent inhibition of ASIC1a by diminazene.

<p>(A) Representative ramp tracings from an oocyte expressing ASIC1a before and after diminazene. Ramps from +60 to -140 mV with a duration of 500 msec were generated in the absence and presence of diminazene (1 nM and 1 μM). ASIC currents were evoked by changing the extracellular pH from 8 to 6.5. Note that the inhibition of ASIC1a by 1 μM diminazene displays strong voltage dependence. (B) Normalized proton-evoked currents from oocytes expressing ASIC1a in the absence and presence of diminazene. Proton-evoked currents were elicited as indicated above in B. Proton-evoked currents measured in the presence of diminazene were normalized to the proton-evoked current measured at -120 mV before diminazene (n = 7–22). (C) Diminazene IC₅₀ at each voltage was calculated from dose-response curves. The calculated diminazene IC₅₀ was 2.48 μM (CI 1.48–4.04 μM, n = 7–22) at—40 mV, 1.82 μM (CI 1.16–2.75 μM, n = 7–22) at—60 mV, 1.41 μM (CI 0.91–2.10 μM, n = 7–22) at -80 mV, 0.99 μM (CI 0.63–1.49 μM, n = 7–22) at -100 mV, and 0.78 μM (CI 0.52–1.13 μM, n = 7–22) at -120 mV. (D) Diminazene IC₅₀ shows a strong dependence with the membrane potential. Log IC₅₀ values (C) were plotted as a function of the membrane potential. Data represent log IC₅₀ ± SEM. Data were fitted by linear regression (slope 0.0063 ± 0.0002, r² = 0.997, p<0.0001).