Effects of three alkoxypsoralens on voltage gated ion channels in Ranvier nodes

T. Düring, F. Gerst, W. Hänsel, Heike Wulff, E. Koppenhöfer

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The effects of the phototoxic K+- channel blockers 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP) on Ranvier nodes were compared to those of 5,8-diethoxypsoralen (5,8-EOP) by means of the Hodgkin-Huxley formalism. When these test substances were added individually to the bathing solution (8-MOP: 100 μmol/1; 5-MOP: 50 μmol/1; 5,8-EOP: 10 μmol/1) the following completely reversible effects were observed: 1. 8-MOP, caused a nearly potential-independent decrease of the sodium permeability, P′Na, by ca. 17%. 5-MOP and 5,8-EOP merely decreased the maximal value of P′Na, by ca. 12 and 8% respectively, whereas with weak depolarisations P′Na was unchanged. 2. In the tested potential range the potassium permeability, P′K ,was caused to decrease by ca. 9% by 8-MOP, ca. 21% by 5-MOP and ca. 19% by 5,8-EOP. 3. The potassium currents acquired a phasic time course previously described for 8-MOP and 5-MOP. They reached a relative maximum and approached a lower steady-state value, k∞, with a time constant τk at V = 120 mV of about 16 ms (8-MOP), 20 ms (5-MOP) and 94 ms (5,8-EOP). To obtain dose-response relations the drug-induced effects on peak P′K and on the steady state value, k∞, were measured. The corresponding apparent dissociation constants (in μmol/1) were 66.6 and 80.1 (for 8-MOP), 87.6 and 25.8 (for 5-MOP), and 13.5 and 6.5 (for 5,8-EOP). In view of the similarity of the actions of 5-MOP and 5,8-EOP as well as the fact that 5,8-EOP is not phototoxic, in future 5,8-EOP may well prove to be a particularly suitable K+-channel blocker for the symptomatic therapy of multiple sclerosis and other demyelinating diseases.

Original languageEnglish (US)
Pages (from-to)345-364
Number of pages20
JournalGeneral Physiology and Biophysics
Volume19
Issue number4
StatePublished - Dec 2000
Externally publishedYes

Keywords

  • Demyelinating diseases
  • K-channel blockers
  • Node of Ranvier
  • Psoralens

ASJC Scopus subject areas

  • Physiology
  • Biophysics

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    Düring, T., Gerst, F., Hänsel, W., Wulff, H., & Koppenhöfer, E. (2000). Effects of three alkoxypsoralens on voltage gated ion channels in Ranvier nodes. General Physiology and Biophysics, 19(4), 345-364.