An Attempt to Distinguish between the Actions of Neuromuscular Blocking Drugs on the Acetylcholine Receptor and on Its Associated Ionic Channel

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 (t1/2) of endplate current...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 1980-08, Vol.77 (8), p.5003-5007
Hauptverfasser: Lambert, Jeremy J., Volle, Robert L., Henderson, Edward G.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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 (t1/2) of endplate currents (e.p.c.s) recorded at a holding potential (Vm) of -90 mV was significantly shorter in endplates treated with lobeline (50 μ M; mean t1/2± SEM=0.41 ± 0.02 ms) or tubocurarine (11.4 μ M; t1/2=0.64± 0.04 ms) than in those treated with Mg2+(13 mM; t1/2=1.39± 0.11 ms) or a low concentration of tubocurarine (3 μ M; t1/2=0.87± 0.05 ms). Similarly, lobeline (10 μ M) shortened the t1/2of 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 t1/2of e.p.c.s recorded from preparations treated with Mg2+(13mM), tubocurarine at low concentrations (3 μ M), or untreated miniature e.p.c.s was logarithmically related to Vm, being slower at more hyperpolarized values. By contrast, the t1/2s of e.p.c.s recorded in either lobeline (50 μ M) or tubocurarine (11.4 μ M) were independent of voltage in the range -150 to -80 mV. The ability of lobeline to shorten t1/2and to remove the voltage dependence of t1/2was 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 μ M) 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 t1/2of 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.77.8.5003