Modulation of voltage-gated channel currents by harmaline and harmane

Frank Splettstoesser, Udo Bonnet, Martin Wiemann, Dieter Bingmann, Dietrich Büsselberg

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40 Citations (Scopus)

Abstract

Harmala alkaloids are endogenous substances, which are involved in neurodegenerative disorders such as M. Parkinson, but some of them also have neuroprotective effects in the nervous system. While several sites of action at the cellular level (e.g. benzodiazepine receptors, 5-HT and GABA A receptors) have been identified, there is no report on how harmala alkaloids interact with voltage-gated membrane channels. The aim of this study was to investigate the effects of harmaline and harmane on voltage-activated calcium- (I Ca(V)), sodium- (I Na(V)) and potassium (I K(V))-channel currents, using the whole-cell patchclamp method with cultured dorsal root ganglion neurones of 3-week-old rats. Currents were elicited by voltage steps from the holding potential to different command potentials. Harmaline and harmane reduced I Ca(V), I Na(V) and I K(V) concentration-dependent (10-500 μM) over the voltage range tested. I Ca(V) was reduced with an IC 50 of 100.6 μM for harmaline and by a significantly lower concentration of 75.8 μM (P < 0.001, t-test) for harmane. The Hill coefficient was close to 1. Threshold concentration was around 10 μM for both substances. The steady state of inhibition of I Ca(V) by harmaline or harmane was reached within several minutes. The action was not use dependent and at least partly reversible. It was mainly due to a reduction in the sustained calcium channel current (I Ca(L+N)), while the transient voltage-gated calcium channel current (I Ca(T)) was only partially affected. We conclude that harmaline and harmane are modulators of I Ca(V) in vitro. This might be related to their neuroprotective effects.

Original languageEnglish
Pages (from-to)52-58
Number of pages7
JournalBritish Journal of Pharmacology
Volume144
Issue number1
DOIs
Publication statusPublished - 1 Jan 2005

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Keywords

  • Dorsal root ganglion neurones
  • Harmaline
  • Harmane
  • Rat
  • Voltage-gated calcium currents
  • Voltage-gated potassium currents
  • Voltage-gated sodium currents

ASJC Scopus subject areas

  • Pharmacology

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