Quinacrine Blocks PrP (106-126)-Formed Channels

Peter V. Farrelly, Bronwyn L. Kenna, Karina L. Laohachai, Randa Bahadi, Mario Salmona, Gianluigi Forloni, Joseph I. Kourie

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

We investigated the action of the acridine derivative, quinacrine (QC), which has been shown to act as a noncompetitive channel inhibitor. The main effects of QC are voltage- and concentration-dependent changes in the kinetics of the prion protein fragment (PrP[106-126])-formed cation channels. The current-voltage relationships show that the maximal current (I) was not affected whereas the physiologically important mean current (I′) was reduced as a result of changes in channel kinetics. These findings suggest that QC acts on the open state of the channels. The half-inhibitory concentration (IC 50) for the dose-dependent effects of [QC] cis on the kinetic parameters of the PrP(106-126)-formed cation channel shows a reduction in the ratios P o(QC)/P o, F o(QC)/F o, and T o(QC)/T o, whereas T c(QC)/T c increases. Of these ratios, P o(QC)/P o, was more sensitive than the others. The corresponding IC 50 for these ratios were 51, 94, 86, and 250 μM QC, respectively. The QC-induced changes in the kinetic parameters were more apparent at positive voltages. IC 50 values for P o were 95, 75, and 51 μM at +20, +80, and +140 mV, respectively. The fact that QC induced changes in the kinetics of this channel, although the conductance of the channel remained unchanged, indicates that QC may bind at the mouth of the channel via a mechanism known as fast channel block. The QC-induced changes in the kinetic parameters of this channel suggest that they are pathophysiologically significant because these channels could be the mechanisms by which amyloids induce membrane damage in vivo.

Original languageEnglish
Pages (from-to)934-941
Number of pages8
JournalJournal of Neuroscience Research
Volume74
Issue number6
DOIs
Publication statusPublished - Dec 15 2003

Fingerprint

Quinacrine
Cations
Acridines
Amyloid
Inhibitory Concentration 50

Keywords

  • Aggregation
  • Amyloids
  • Ion channels
  • Mechanisms of membrane damage
  • Misfolded proteins
  • Neurodegenerative disease
  • Prion diseases

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Farrelly, P. V., Kenna, B. L., Laohachai, K. L., Bahadi, R., Salmona, M., Forloni, G., & Kourie, J. I. (2003). Quinacrine Blocks PrP (106-126)-Formed Channels. Journal of Neuroscience Research, 74(6), 934-941. https://doi.org/10.1002/jnr.10849

Quinacrine Blocks PrP (106-126)-Formed Channels. / Farrelly, Peter V.; Kenna, Bronwyn L.; Laohachai, Karina L.; Bahadi, Randa; Salmona, Mario; Forloni, Gianluigi; Kourie, Joseph I.

In: Journal of Neuroscience Research, Vol. 74, No. 6, 15.12.2003, p. 934-941.

Research output: Contribution to journalArticle

Farrelly, PV, Kenna, BL, Laohachai, KL, Bahadi, R, Salmona, M, Forloni, G & Kourie, JI 2003, 'Quinacrine Blocks PrP (106-126)-Formed Channels', Journal of Neuroscience Research, vol. 74, no. 6, pp. 934-941. https://doi.org/10.1002/jnr.10849
Farrelly, Peter V. ; Kenna, Bronwyn L. ; Laohachai, Karina L. ; Bahadi, Randa ; Salmona, Mario ; Forloni, Gianluigi ; Kourie, Joseph I. / Quinacrine Blocks PrP (106-126)-Formed Channels. In: Journal of Neuroscience Research. 2003 ; Vol. 74, No. 6. pp. 934-941.
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AU - Salmona, Mario

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