Inhibition of voltage-gated Na(+) currents in sensory neurones by the sea anemone toxin APETx2

Autor: Maxime G, Blanchard, Lachlan D, Rash, Stephan, Kellenberger
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
Sodium Channels/metabolism
Patch-Clamp Techniques
Sensory Receptor Cells
Nerve Tissue Proteins/antagonists & inhibitors
Sodium Channels/genetics
Nerve Tissue Proteins
Sodium Channel Blockers/pharmacology
In Vitro Techniques
Cnidarian Venoms/pharmacology
Sodium Channels
NAV1.8 Voltage-Gated Sodium Channel
Xenopus laevis
Cnidarian Venoms
Ganglia
Spinal
Sodium Channels/drug effects
Animals
Nerve Tissue Proteins/genetics
Recombinant Proteins/genetics
Ganglia
Spinal/cytology
Rats
Wistar
Sensory Receptor Cells/metabolism
Ganglia
Spinal/metabolism
Oocytes/metabolism
Oocytes/drug effects
Research Papers
Ion Channel Gating/drug effects
Recombinant Proteins
Rats
Acid Sensing Ion Channels
Ganglia
Spinal/drug effects
Sea Anemones
Membrane transport and intracellular motility Renal disorder [NCMLS 5]
Recombinant Proteins/antagonists & inhibitors
Oocytes
Female
Sensory Receptor Cells/drug effects
Ion Channel Gating
Sodium Channel Blockers
Zdroj: British Journal of Pharmacology, vol. 165, no. 7, pp. 2167-2177
British journal of pharmacology
British Journal of Pharmacology, 165, 2167-77
British Journal of Pharmacology, 165, 7, pp. 2167-77
ISSN: 0007-1188
Popis: Item does not contain fulltext BACKGROUND AND PURPOSE: APETx2, a toxin from the sea anemone Anthropleura elegantissima, inhibits acid-sensing ion channel 3 (ASIC3)-containing homo- and heterotrimeric channels with IC(50) values < 100 nM and 0.1-2 microM respectively. ASIC3 channels mediate acute acid-induced and inflammatory pain response and APETx2 has been used as a selective pharmacological tool in animal studies. Toxins from sea anemones also modulate voltage-gated Na(+) channel (Na(v) ) function. Here we tested the effects of APETx2 on Na(v) function in sensory neurones. EXPERIMENTAL APPROACH: Effects of APETx2 on Na(v) function were studied in rat dorsal root ganglion (DRG) neurones by whole-cell patch clamp. KEY RESULTS: APETx2 inhibited the tetrodotoxin (TTX)-resistant Na(v) 1.8 currents of DRG neurones (IC(50) , 2.6 microM). TTX-sensitive currents were less inhibited. The inhibition of Na(v) 1.8 currents was due to a rightward shift in the voltage dependence of activation and a reduction of the maximal macroscopic conductance. The inhibition of Na(v) 1.8 currents by APETx2 was confirmed with cloned channels expressed in Xenopus oocytes. In current-clamp experiments in DRG neurones, the number of action potentials induced by injection of a current ramp was reduced by APETx2. CONCLUSIONS AND IMPLICATIONS: APETx2 inhibited Na(v) 1.8 channels, in addition to ASIC3 channels, at concentrations used in in vivo studies. The limited specificity of this toxin should be taken into account when using APETx2 as a pharmacological tool. Its dual action will be an advantage for the use of APETx2 or its derivatives as analgesic drugs. 01 april 2012
Databáze: OpenAIRE
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