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°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 μM; mean t( 1/2 ) ± SEM = 0.41 ± 0.02 ms) or tubocurarine (11.4 μM; t( 1/2 ) = 0.64 ± 0.04 ms) than in those treated with Mg2+ (13 mM; t( 1/2 ) = 1.39 ± 0.11 ms) or a low concentration of tubocurarine (3 μM; t( 1/2 ) = 0.87 ± 0.05 ms). Similarly, lobeline (10 μM) 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 Mg2+ (13 mM), tubocurarine at low concentrations (3 μM), 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 ) of e.p.c.s recorded in either lobeline (50 μM) or tubocurarine (11.4 μM) 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 Mg2+ (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 μM) and Ca2+ (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 tubucurarine 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.
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Issue number||8 I|
|Publication status||Published - 1 Jan 1980|