The injection of tetraethylammonium chloride into the giant axon of the squid prolongs the action potential and eliminates most of the late current under voltage-clamp. Experiments on fibers in an external medium of high potassium ion concentration demonstrate that injected tetraethylammonium chloride causes rectification of the instantaneous current-voltage curve for potassium by excluding outward current. This interference with the flow of outward potassium ion current underlies the prolongation of the action potential seen in tetraethylammonium-injected fibers.

Voltage-clamp studies on intact and internally perfused squid giant axons demonstrate that ammonium can substitute partially for either sodium or potassium. Ammonium carries the early transient current with 0.3 times the permeability of sodium and it carries the delayed current with 0.3 times the potassium permeability. The conductance changes observed in voltage clamp show approximately the same time course in ammonium solutions as in the normal physiological solutions. These ammonium ion permeabilities aceount for the known effects of ammonium on nerve excitability. Experiments with the drugs tetrodotoxin (TTX) and tetraethyl ammonium chloride (TEA) demonstrate that these molecules block the early and late components of the current selectively, even when both components are carried by the same ion, ammonium.

The effects of several alcohols on the resting potential, action potential, and voltage-clamp currents of the squid giant axon have been measured. All the alcohols employed are similar in that they depress maximum sodium conductance much more than maximum potassium conductance. Octyl alcohol differs from the others (C 2 through Cs) in that it has less tendency to depolarize the axon. Depolarization is always accompanied by a decrease of gr near the resting potential, such that the ratio gK/glek is decreased. Steadystate inactivation of the sodium ion current is unaffected by alcohols, as is membrane capacity. Resting membrane conductance is usually decreased by alcohols. The findings are discussed in relation to work on monomolecular films.

A new dissection procedure for preparing Myxicola giant axons for observation under voltage clamp is described. Preparation time is generally 40--45 rain. 65-70 % of the preparations attempted may be brought through the entire procedure, including insertion of the long internal electrode, and support an initial action potential amplitude of 100 my or greater. Mean values for axon diameter, resting membrane potential, action potential amplitude, maximum peak inward transient current, and resting membrane resistance are 560 #, --66.5 my, 112 my, 0.87 ma/cm ~, and 1.22 Kl2 cm 2, respectively. Cut branches do not seem to be a problem in this preparation. Behavior under voltage clamp is reasonably stable over several hours. Reductions in maximum inward transient current of 10% and in steady-state current of 5-10% are expected in the absence of any particular treatment. Tetrodotoxin blocks the action potential and both the inward and outward transient current, but has no effect on either the resting membrane potential or the steady-state current. This selective action of tetrodotoxin on the transient current is taken as an indication that this current component is probably carried by Na.