The interactions of 9-aminoacridine with ionic channels were studied in internally perfused squid axons. The kinetics of block of Na channels with 9- aminoacridine varies depending on the voltage-clamp pulses and the state of gating machinery of Na channels. In an axon with intact h gate, the block exhibits frequency- and voltage-dependent characteristics. However, in the pronase-per- fused axon, the frequency-dependent block disappears, whereas the voltage- dependent block remains unchanged. A time-dependent decrease in Na currents indicative of direct block of Na channel by drug molecule follows a single exponential function with a time constant of 2.0 ± 0.18 and 1.0 ± 0.19 ms (at 10°C and 80 mV) for 30 and 100 µM 9-aminoacridine, respectively. A steady-state block can be achieved during a single 8-ms depolarizing pulse when the h gate has been removed. The block in the h-gate intact axon can be achieved only with multiple conditioning pulses. The voltage-dependent block suggests that 9-aminoacridine binds to a site located halfway across the membrane with a dissociation constant of 62 µM’ at 0 mV. 9-Aminoacridine also blocks K channels, and the block is time- and voltage-dependent. © 1979, Rockefeller University Press., All rights reserved.
