Channel activity of deamidated isoforms of prion protein fragment 106-126 in planar lipid bilayers

Joseph I. Kourie*, Peter V. Farrelly, Christine L. Henry

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    29 Citations (Scopus)


    Using the lipid bilayer technique, we have found that age-related derivatives, PrP[106-126] (L-Asp108) and PrP[106-126] (L-iso-Asp108), of the prion protein fragment 106-126 (PrP[106-126] (Asn108)) form heterogeneous ion channels. The deamidated isoforms, PrP[106-126] (L-Asp108) and PrP[106-126] (L-iso-Asp108), showed no enhanced propensity to form heterogeneous channels compared with PrP[106-126] (Asn108). One of the PrP[106-126] (L-Asp108)- and PrP[106-126] (L-iso-Asp108)-formed channels had three kinetic modes. The current-voltage (I-V) relationship of this channel, which had a reversal potential, Erev, between -40 and -10 mV close to the equilibrium potential for K+ (EK -35 mV), exhibited a sigmoidal shape. The value of the maximal slope conductance (gmax) was 62.5 pS at positive potentials between 0 and 140 mV. The probability (Po) and the frequency (Fo) of the channel being open had inverted and bell-shaped curves, respectively, with a peak at membrane potential (Vm) between -80 and +80 mV. The mean open and closed times (To and Tc) had inverted bell-shaped curves. The biophysical properties of PrP[106-126] (L-Asp108)- and PrP[106-126] (L-iso-Asp108)-formed channels and their response to Cu2+ were similar to those of channels formed with PrP[106-126] (Asn108). Cu2+ shifted the kinetics of the channel from being in the open state to a "burst state" in which rapid channel activities were separated by long durations of inactivity. The action of Cu2+ on the open channel activity was both time-dependent and voltage-dependent. The fact that Cu2+ induced changes in the kinetics of this channel with no changes in the conductance of the channel indicated that Cu2+ binds at the mouth of the channel. Consistently with the hydrophilic and structural properties of PrP[106-126], the Cu2+-induced changes in the kinetic parameters of this channel suggest that the Cu2+ binding site could be located at M109 and H111 of this prion fragment.

    Original languageEnglish
    Pages (from-to)214-220
    Number of pages7
    JournalJournal of Neuroscience Research
    Issue number2
    Publication statusPublished - 15 Oct 2001


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