The effects of lobeline and tubocurarine on the voltage-clamped endplates of frog sartorius and cutaneous pectoris muscles were examined at room temperature (20-23 degrees C). Like tubocurarine, lobeline causes nondepolarizing neuromuscular blockade. The half-time of decay (t((1/2))) of endplate currents (e.p.c.s) recorded at a holding potential (V(m)) of -90 mV was significantly shorter in endplates treated with lobeline (50 muM; mean t((1/2)) +/- SEM = 0.41 +/- 0.02 ms) or tubocurarine (11.4 muM; t((1/2)) = 0.64 +/- 0.04 ms) than in those treated with Mg(2+) (13 mM; t((1/2)) = 1.39 +/- 0.11 ms) or a low concentration of tubocurarine (3 muM; t((1/2)) = 0.87 +/- 0.05 ms). Similarly, lobeline (10 muM) shortened the t((1/2)) of untreated miniature e.p.c.s by 35%; tubocurarine, however, abolished miniature e.p.c.s at the concentration required to observe its actions on e.p.c. decay kinetics. The t((1/2)) of e.p.c.s recorded from preparations treated with Mg(2+) (13 mM), tubocurarine at low concentrations (3 muM), or untreated miniature e.p.c.s was logarithmically related to V(m), being slower at more hyperpolarized values. By contrast, the t((1/2))s of e.p.c.s recorded in either lobeline (50 muM) or tubocurarine (11.4 muM) were independent of voltage in the range -150 to -80 mV. The ability of lobeline to shorten t((1/2)) and to remove the voltage dependence of t((1/2)) was partially antagonized by Mg(2+) (13 mM). As expected, when lobeline or tubocurarine was removed from the bath or when acetylcholine release from the motor nerve terminals was increased by 4-aminopyridine (20 muM) and Ca(2+) (10 mM) (in the presence of lobeline or tubocurarine), the amplitude of e.p.c.s increased as a function of time. However, the t((1/2)) of the decay phase of the e.p.c.s remained shortened (i.e., unaltered from the earlier treatment). These results suggest that both tubocurarine and lobeline have at least two distinct postjunctional actions including: (i) a block of the acetylcholine receptor and (ii) a block of the ionic channel associated with the acetylcholine receptor.