Background and purpose: Cisplatin drives specific types of tumour cells to apoptosis.

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Material Supplementary 4.DC1http://www.jimmunol.org/content/suppl/2010/06/23/jimmunol.090324

1 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. 2 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 voltagegated membrane channels. 3 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. 4 Harmaline and harmane reduced I Ca(V) , I Na(V) and I K(V) concentration-dependent (10-500 mM) over the voltage range tested. I Ca(V) was reduced with an IC 50 of 100.6 mM for harmaline and by a significantly lower concentration of 75.8 mM (Po0.001, t-test) for harmane. The Hill coefficient was close to 1. Threshold concentration was around 10 mM for both substances. 5 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. 6 It was mainly due to a reduction in the sustained calcium channel current (I Ca (L þ N) ), while the transient voltage-gated calcium channel current (I Ca(T) ) was only partially affected. 7 We conclude that harmaline and harmane are modulators of I Ca(V) in vitro. This might be related to their neuroprotective effects.

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