A 0.1-700 HZ CURRENT THROUGH A VOLTAGE-CLAMPED PORE - CANDIDATE PROTEIN FOR INITIATOR OF NEURAL OSCILLATIONS

A protein of mass 7643 Da and sequence identical to that of subunit c, the pore part, of the mitochondrial adenosine triphosphate synthase c omplex, was co-purified with cholesterol in crystals formed from a chl oroform/methanol extract of bovine brain gray matter plasma membranes. Reconstitution of the protein-containing crystals in phospholipid bil ayers and assay of current by patch-clamp analysis, showed an oscillat ing cation current at constant voltage, typically of frequency 0.5-200 Hz. The ceroid-lipofuscinoses state in mammals and man (fatten diseas e), in which subunit c accumulates in lysosomes, affords a rich source of the protein. Pure subunit c from affected sheep liver (in the abse nce of cholesterol) was also assayed, the current displaying identical sodium oscillations to those of brain crystals. The results suggest t hat if a protein similar to subunit c resides in the plasma membrane o f neural cells, it could be responsible for spontaneous oscillations i n brain tissue. The relevance of these results to the pathogenesis of Batten disease is discussed. (C) 1997 Elsevier Science B.V.