Blockage of resting potassium conductance in frog muscle fibers by a toxin isolated from the sponge Haliclona viridis.

A fraction able to irreversibly depolarize sartorius muscle fibers was isolated from the marine sponge. The resting potential is decreased from -84 (-85, -83) mV (median and its 95% confidence interval) to -40 (-46, -30) mV. The fibers depolarized by the sponge toxin are restored to -54 (-57, -49) mV when external sodium is replaced by Tris or to -52 (-57, -47) mV when calcium is removed from the saline solution in the presence of 1 mM EDTA and 1 microM tetrodotoxin. Tetrodotoxin alone (1 micron) has no effect on the depolarization [-43 (-50, -37) mV] produced by the sponge and 5 mM manganese only repolarizes the fibers to -48 (-55, -40) mV. The depolarization is potentiated [-28 (-33, -23) mV] when chloride is replaced by glutamate in the external solution. The access resistance of the muscle fibers is not significantly changed from its control value of 2.74 (2.28, 3.30) M omega when toxin is added. By contrast 20 mM K+ superfused to the fibers changes membrane potential to -44 (-46, -42) mV and decreases access resistance to 1.99 (1.38, 2.87) M omega. The toxin is devoid of any effect on the endplate, since the depolarization of the postsynaptic membrane is identical to the extrajunctional area, and miniature endplate potentials of normal shape and high frequency are easy to record from toxin treated fibers. The action potential is not modified by the toxin. The toxin is a small polar compound insoluble in acetone and is likely to act on a receptor located on the outer phase of the membrane. The biological activity appears as a peak on elution with 1 M acetic acid on Bio Gel P2.