Current-dependent block of nerve membrane sodium channels by paragracine.

Paragracine, isolated from the coelenterate species Parazoanthus gracilis, selectively blocks sodium channels of squid axon membranes in a frequency-dependent manner. The blocking action depends on the direction and magnitude of the sodium current rather than on the absolute value of the membrane potential. Paragracine blocks the channels only from the axoplasmic side and does so only when the current is in the outward direction. This block may be reversed by generating inward sodium currents. In axons in which sodium inactivation has been removed by pronase, the frequency-dependent block persists, and a slow time-dependent block is observed. A slow interaction with its binding site in the channel may account for the frequency-dependent block.