Dynamics of 9-aminoacridine block of sodium channels in squid axons.
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-perfused 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 degrees C and 80 m V) for 30 and 100 microM 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 microM at 0 m V. 9-Aminoacridine also blocks K channels, and the block is time- and voltage-dependent.
D000166:Acridines / Q000494:pharmacology*; D000200:Action Potentials; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D049832:Decapodiformes / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D008564:Membrane Potentials; D008954:Models, Biological; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D000166:Acridines; D007473:Ion Channels; D012964:Sodium; D011188:Potassium