A 0.1-700 Hz current through a voltage-clamped pore: candidate protein for initiator of neural oscillations.

ABSTRACT

A protein of mass 7643 Da and sequence identical to that of subunit c, the pore part, of the mitochondrial adenosine triphosphate synthase complex, was co-purified with cholesterol in crystals formed from a chloroform/methanol extract of bovine brain gray matter plasma membranes. Reconstitution of the protein-containing crystals in phospholipid bilayers and assay of current by patch-clamp analysis, showed an oscillating cation current at constant voltage, typically of frequency 0.5-200 Hz. The ceroid-lipofuscinoses state in mammals and man (Batten disease), in which subunit c accumulates in lysosomes, affords a rich source of the protein. Pure subunit c from affected sheep liver (in the absence of cholesterol) was also assayed, the current displaying identical sodium oscillations to those of brain crystals. The results suggest that if a protein similar to subunit c resides in the plasma membrane of neural cells, it could be responsible for spontaneous oscillations in brain tissue. The relevance of these results to the pathogenesis of Batten disease is discussed.