An attempt to distinguish between the actions of neuromuscular blocking drugs on the acetylcholine receptor and on its associated ionic channel

Jeremy J. Lambert, Robert L. Volle, Edward G. Henderson

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5003-5007
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume77
Issue number8 I
DOIs
Publication statusPublished - 1 Jan 1980

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