Abstract
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, E~rev~, between –40 and –10 mV close to the equilibrium potential for K^+^ (E~K~ –35 mV), exhibited a sigmoidal shape. The value of the maximal slope conductance (g~max~) was 62.5 pS at positive potentials between 0 and 140 mV. The probability (P~o~) and the frequency (F~o~) of the channel being open had inverted and bell‐shaped curves, respectively, with a peak at membrane potential (V~m~) between –80 and +80 mV. The mean open and closed times (T~o~ and T~c~) 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 Cu^2+^ were similar to those of channels formed with PrP[106–126] (Asn108). Cu^2+^ 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 Cu^2+^ on the open channel activity was both time‐dependent and voltage‐dependent. The fact that Cu^2+^ induced changes in the kinetics of this channel with no changes in the conductance of the channel indicated that Cu^2+^ binds at the mouth of the channel. Consistently with the hydrophilic and structural properties of PrP[106–126], the Cu^2+^‐induced changes in the kinetic parameters of this channel suggest that the Cu^2+^ binding site could be located at M~109~ and H~111~ of this prion fragment. J. Neurosci. Res. 66:214–220, 2001. © 2001 Wiley‐Liss, Inc.