H. Monoi et al., Poly-(L)-glutamine forms cation channels: Relevance to the pathogenesis ofthe polyglutamine diseases, BIOPHYS J, 78(6), 2000, pp. 2892-2899
We report that long-chain poly-L-glutamine forms cation-selective channels
when incorporated into artificial planar lipid bilayer membranes. The chann
el was permeable to alkali cations and H+ ions and virtually impermeable to
anions; the selectivity sequence based on the single-channel conductance w
as H+ much greater than Cs+ > K+ > Na+. The cation channel was characterize
d by long-lived open states (often lasting for several minutes to tens of m
inutes) interrupted by brief closings. The appearance of the channel depend
ed critically on the length of polyglutamine chains; ion channels were obse
rved with 40-residue stretches, whereas no significant conductance changes
were detected with 29-residue tracts. The channel-forming threshold length
of poly-L-glutamine was thus between 29 and 40 residues. A molecular mechan
ics calculation suggests a mu-helix (Monoi, 1995. Biophys. J. 69:1130-1141)
as a candidate molecular structure of the channel. The channel-forming nat
ure of long-chain poly-L-glutamine may provide a clue to the elucidation of
the pathogenetic mechanism of the polyglutamine diseases, a group of inher
ited neurodegenerative disorders including Huntington's disease.