Inhibition of acetylcholine release from presynaptic terminals of skate electric organ by calcium channel antagonists: a detailed pharmacological study
| Autor: | D Bowman, Michael J. Dowdall, C M Richardson |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
End-plate potential
chemistry.chemical_element In Vitro Techniques Neurotransmission Calcium Pharmacology Receptors Presynaptic complex mixtures Cellular and Molecular Neuroscience Nifedipine medicine Animals Skates Fish Evoked Potentials Electric Organ Voltage-dependent calcium channel Chemistry Calcium channel Calcium Channel Blockers Acetylcholine Electric Stimulation Electrophysiology Kinetics Potassium Verapamil medicine.drug |
| Zdroj: | Neuropharmacology. 35:1537-1546 |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/s0028-3908(96)00107-4 |
| Popis: | Release of acetylcholine (ACh) from the presynaptic terminals in skate electric organ was tested for its sensitivity to calcium channel antagonists. A pharmacological profile was established by measuring inhibition of K(+)-stimulated release of [3H]ACh from prelabelled tissue slices. Peptide antagonists of N-type (omega-conotoxins GVIA and MVIIA) and P-type (omega-agatoxin-IVA) channels had no effect, whereas both omega-conotoxins MVIIC and SVIB produced concentration-dependent inhibition and could completely block ACh release. omega-Conotoxin GVIA and omega-agatoxin IVA did not attenuate the block by omega-conotoxin MVIIC. The inorganic ions, Cd2+ and Ni2+, also produced a full inhibition of release (Cd2+ > > Ni2+) and Gd3+ a partial one. Drugs targeting L-type channels (diltiazem, nifedipine and verapamil) at low microM concentrations and a synthetic analogue of the polyamine toxin from funnel web spider venom (sFTX) at 1 mM were all non-inhibitory. Inhibition by omega-conotoxins MVIIC (IC50 25 nM) and SVIB (IC50 500 nM) was reversible and modulated by external concentrations of Ca2+. Inhibitory potency was increased by lowering and decreased by elevating external Ca2+. This "antagonistic" effect of Ca2+ was also seen with Cd2+ inhibition. The inhibitory potency of omega-conotoxin MVIIC was unaffected by predepolarisation. End plate potentials generated by release of endogenous ACh in electrically-stimulated slices were also reversibly blocked by Cd2+ and omega-conotoxins MVIIC and SVIB but were unaffected by omega-conotoxin GVIA and omega-agatoxin IVA. It is concluded that ACh release in skate electric organ depends on presynaptic calcium channels which have different pharmacological properties from established sub-types. |
| Databáze: | OpenAIRE |
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