Hexamethonium- and methyllycaconitine-induced changes in acetylcholine release from rat motor nerve terminals

L Tian, C Prior, J Dempster, I G Marshall

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Abstract

The neuronal nicotinic receptor antagonists hexamethonium and methyllycaconitine (MLA) have been used to study the putative prejunctional nicotinic ACh receptors (AChRs) mediating a negative-feedback control of ACh release from motor nerve terminals in voltage-clamped rat phrenic nerve/ hemidiaphragm preparations. Hexamethonium (200 microM), but not MLA (0.4-2.0 microM), decreased the time constant of decay of both endplate currents (e.p.cs) and miniature endplate currents (m.e.p.cs), indicating endplate ion channel block with hexamethonium. However, driving function analysis and reconvolution of e.p.cs and m.e.p.cs indicated that this ion channel block did not compromise the analysis of e.p.c. quantal content. At low frequencies of stimulation (0.5-2 Hz), hexamethonium (200 microM) and MLA (2.0 microM) increased e.p.c. quantal content by 30-40%. At high frequencies (50-150 Hz) neither compound affected e.p.c. quantal content. All effects on quantal content were paralleled by changes in the size of the pool of quanta available for release. The low frequency augmentation of e.p.c. quantal content by hexamethonium was absent when extracellular [Ca2+] was lowered from 2.0 to 0.5 mM. At the concentrations studied, MLA and hexamethonium produced a small (10-20%) decrease in the peak amplitude of m.e.p.cs. Neither apamin (100 nM) nor charybdotoxin (80 nM) had effects on spontaneous or nerve evoked current amplitudes at any frequency of stimulation. Thus the ability of nicotinic antagonists to augment e.p.c. quantal content is not due to inhibition of Ca(2+)-activated K(+)-channels. We suggest that hexamethonium and MLA increase evoked ACh release by blocking prejunctional nicotinic AChRs. These receptors exert a negative feedback control over evoked ACh release and are probably of the alpha-bungarotoxin-insensitive neuronal type.
Original languageEnglish
Pages (from-to)1025-1034
Number of pages10
JournalBritish Journal of Pharmacology
Volume122
Issue number6
DOIs
Publication statusPublished - Nov 1997

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Keywords

  • acetylcholin
  • aconitine
  • animals
  • calcium
  • evoked potentials
  • hexamethonium
  • ion channel gating
  • male
  • motor endplate
  • nicotinic antagonists
  • potassium channel blockers
  • rats
  • sprague-dawley rats

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