This study aims to test the hypothesis that the hyperexcitability of neuronal membranes in neuropsychiatric disorders which involve disturbances of movement, mood and cognition arises from the ion-channel activity of an endogenous tetanus toxin-like molecule. The hypothesis formulated is unique in so far as it focuses on the clinical and pathophysiological similarities between some forms of schizophrenic psychosis and epilepsy with tetanus, and its novelty is the distinct suggestion of the existence of an endogenous peptide that mimics the known channel activity of tetanus toxin. The experimental strategy is based on the critical concept that a specific entity of predicted amino acid sequence adopts an amphipathic alpha-helical structure in neuronal membranes and aggregates to provide a polar pathway for ionic conduction through the non-polar interior of the bilayer membrane.
Gambale, F; Montal, M (1990) Voltage-gated sodium channels expressed in the human cerebellar medulloblastoma cell line TE671. Brain Res Mol Brain Res 7:123-9 |
Rauch, G; Gambale, F; Montal, M (1990) Tetanus toxin channel in phosphatidylserine planar bilayers: conductance states and pH dependence. Eur Biophys J 18:79-83 |
Montal, M (1990) Channel protein engineering. An approach to the identification of molecular determinants of function in voltage-gated and ligand-regulated channel proteins. Ion Channels 2:1-31 |
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