Modification of the Na-dependent action potential in myelinated fibers of rat sciatic nerve exposed to phorbol ester.

Exposure of rat sciatic nerve to the active phorbol 1,2-beta-myristate-13-acetate (b-PMA), but not to the active analogue 4-alpha-phorbol-12,13-didecanoate (a-PDD), is followed by a decrease of the compound action potential amplitude, rate of rise, and conduction velocity, and an increase of the threshold, and of the duration of the refractory period. The effect is concentration-dependent, the Kd being 250 nM. The attenuated Na-dependent action potential is tetrodotoxin (TTX)-sensitive, but after exposure to b-PMA the sensitivity to TTX is decreased from Kd = 45 nM to 400 nM. Action potential depression is larger when Ca is replaced by Mg (but not by Ba), or when Na is replaced by Li. The replacement of K by Cs, or exposure to potassium channel blockers such as 4-aminopyridine (4AP) and tetra-ethyl ammonium (TEA) has no effect. The results indicate that in the myelinated axons of rat sciatic nerve, exposure to b-PMA induces modification of Na channels.