Batten disease and the control of the Fo subunit c pore by cGMP and calcium

• Published in: European journal of paediatric neurology 2001, Vol.5 Suppl A, p.147-150
• Main Authors: McGeoch, J E, Guidotti, G
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - physiology; Calcium - metabolism; Cattle; Cyclic GMP - metabolism; Ion Channel Gating - physiology; Microscopy, Electron; Mitochondrial Proton-Translocating ATPases; Nerve Degeneration - metabolism; Neuronal Ceroid-Lipofuscinoses - metabolism; Proton-Translocating ATPases - metabolism; Proton-Translocating ATPases - ultrastructure; Rats; Sheep
• ISSN: 1090-3798
• DOI: 10.1053/ejpn.2000.0452

Subunit c of ATP synthase functions as a high conductance ion channel, tightly regulated by calcium. We have suggested that the pathogenesis of Batten syndromes involving overaccumulation of subunit c are linked to the protein's ion channel function. In normal electrically excitable tissue the channel could act as a pacer setting nodal voltage via control of cation entry. The channel conductance is controlled by voltage, calcium, cyclic nucleotides and polyamines. We discuss the pathogenic role that subunit c could play in the electrically excitable tissues of retina, brain and heart where Batten neurodegeneration is seen. Focus is given to potential links between subunit c and the known mutant gene products in the Batten diseases, the process of apoptosis, and the requirement of the growing brain for gradients of cGMP, a ligand of the subunit c channel.