Use of geographutoxin II (mu-conotoxin) for the study of neuromuscular transmission in mouse.
1. Endplate potentials (e.p.ps) were investigated in the presence of geographutoxin II (GTXII) in the mouse phrenic nerve diaphragm preparation. This toxin preferentially blocks muscle Na+ channels which allows the study of e.p.ps in the absence of nicotinic receptor antagonists or substances to depress acetylcholine release. 2. GTXII abolished muscle action potentials and antagonized the depolarization of the muscle membrane produced by the crotamine-induced opening of Na+ channels. 3. E.p.ps as large as 19-25 mV were observed after 2-4 micrograms ml-1 GTXII. These concentrations of GTXII did not cause discernible changes of resting membrane potential and frequency and amplitude of miniature e.p.ps. 4. Lower concentrations (1-2 micrograms ml-1) of GTXII caused incomplete blockade of the muscle Na+ channel resulting in exaggerated 'e.p.ps', while higher concentrations of GTXII (8 micrograms ml-1) abolished e.p.ps by a prejunctional effect. 5. Trains of e.p.ps on repetitive stimulation after GTXII neither ran down, as in tubocurarine-treated preparations, nor facilitated, as in low Ca2+ and/or high Mg2+-treated preparations, and were indistinguishable from those of untreated cut muscle preparation. 6. In cut muscle preparations, GTXII did not affect the rise and decay times, amplitude or rundown of e.p.ps. 7. It is concluded that GTXII is a useful agent for studying neuromuscular transmission. This method provides e.p.ps which are neither attenuated nor modified because manipulations that alter transmitter release and postjunctional receptor responses are avoided.
Hong
S J
SJ
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Chang
C C
CC
D000818:Animals; D003964:Diaphragm / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008978:Mollusk Venoms; D009045:Motor Endplate / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D010456:Peptides, Cyclic; D010791:Phrenic Nerve / Q000187:drug effects; D012132:Respiratory Muscles / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D008978:Mollusk Venoms; D010456:Peptides, Cyclic; D013779:Tetrodotoxin; C038094:geographutoxin II