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. J. Neurosci. Res. 66:214–220, 2001. © 2001 Wiley-Liss, Inc.