Inhibitory effects of artemisinin on voltage-gated ion channels in intact nodose ganglion neurones of adult rats

Basic Clin Pharmacol Toxicol. 2007 Apr;100(4):217-24. doi: 10.1111/j.1742-7843.2006.00009.x.

Abstract

Recent data show that artemisinin has anti-arrhythmic and local anaesthetic effects. To better understand the mechanisms, the effects of artemisinin on action potential discharge and voltage-gated ion channels properties were studied on nodose ganglion neurones of adult rats with known sensory afferent fibre type using whole cell patch and vagus nodose slice preparation. The present data show that both depolarization and repolarization of action potentials were markedly inhibited by artemisinin in a concentration- and time-dependent manner in either A-type or C-type nodose ganglion neurones without change in conduction velocity. Both tetrodotoxin-sensitive (TTX-S) Na+ and tetrodotoxin-resistant (TTX-R) Na+ currents were significantly reduced by micro-perfusion of artemisinin; the steady-state half-activation and half-inactivation for both TTX-S and TTX-R Na+ currents were shifted towards the right without changing slope factors. Median inhibition concentration (IC50) are 68.1 microM and 236.2 microM for TTX-S and TTX-R Na+ currents, respectively. Total outward K+ currents from C-type nodose ganglion neurones were blocked by artemisinin 30-300 microM concentration-dependently, IC50 being 104.7 microM. This effect was mimicked by tetraethylammonium 15 mM. Peak currents of N-type Ca2+ channels were also reduced significantly (IC50=344.6 microM) in the presence of artemisinin, which was less effective than that induced by 1 microM omega-conotoxin (CTX) GIVA. Our data demonstrate that depolarization and repolarization of action potentials recorded from either A- or C-type nodose ganglion neurones were inhibited by artemisinin in a concentration- and time-dependent manner, and that this inhibitory effect of artemisinin is probably due to the non-selective inhibition of all major ion channels functionally expressed in nodose ganglion neurones.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Anti-Arrhythmia Agents / pharmacology
  • Anti-Infective Agents / pharmacology
  • Artemisinins / pharmacology*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, N-Type / physiology
  • Dose-Response Relationship, Drug
  • Female
  • Ion Channel Gating / drug effects*
  • Male
  • Neurons / drug effects*
  • Neurons / physiology
  • Nodose Ganglion / cytology
  • Nodose Ganglion / drug effects*
  • Nodose Ganglion / physiology
  • Patch-Clamp Techniques
  • Potassium Channels / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Sesquiterpenes / pharmacology*
  • Sodium Channels / physiology
  • Tetraethylammonium / pharmacology
  • Tetrodotoxin / pharmacology
  • Time Factors
  • omega-Conotoxin GVIA / pharmacology

Substances

  • Anti-Arrhythmia Agents
  • Anti-Infective Agents
  • Artemisinins
  • Calcium Channel Blockers
  • Calcium Channels, N-Type
  • Potassium Channels
  • Sesquiterpenes
  • Sodium Channels
  • Tetrodotoxin
  • Tetraethylammonium
  • omega-Conotoxin GVIA
  • artemisinin