Preferential block of skeletal muscle sodium channels by geographutoxin II, a new peptide toxin from Conus geographus.

The effects of geographutoxin II (GTX II), a novel polypeptide toxin isolated from the marine snail Conus geographus, on nerves and muscles were studied by current clamp and voltage clamp techniques. GTX II (5 X 10(-7) M) abolished the action potential of the guinea pig skeletal muscle without change in the resting potential. However, action potentials of the crayfish giant axon, mouse neuroblastoma N1E-115 cell and guinea pig cardiac muscle were not affected by GTX II even at concentrations higher than 1 X 10(-6) M. In the voltage clamped bullfrog skeletal muscle fiber, sodium currents were almost completely blocked by GTX II (1 X 10(-6) M), and slowly recovered after washout. The time course of sodium currents was not appreciably altered by GTX II. These results suggest that GTX II selectively blocks skeletal muscle sodium channels in much the same way as tetrodotoxin.