A critical role for glycine transporters in hyperexcitability disorders.

Harvey, R.J., Carta, E., Pearce, B.R., Chung, S-K., Supplisson, S., Rees, M.I. and Harvey, K. (2008) A critical role for glycine transporters in hyperexcitability disorders. Frontiers in Molecular Neuroscience, 1 (1). 10.3389/neuro.02.001.2008.

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DOI: 10.3389/neuro.02.001.2008

Abstract

Defects in mammalian glycinergic neurotransmission result in a complex motor disorder characterized by neonatal hypertonia and an exaggerated startle reflex, known as hyperekplexia (OMIM 149400). This affects newborn children and is characterized by noise or touch-induced seizures that result in muscle stiffness and breath-holding episodes. Although rare, this disorder can have serious consequences, including brain damage and/or sudden infant death. The primary cause of hyperekplexia is missense and non-sense mutations in the glycine receptor (GlyR) alpha1 subunit gene (GLRA1) on chromosome 5q33.1, although we have also discovered rare mutations in the genes encoding the GlyR beta subunit (GLRB) and the GlyR clustering proteins gephyrin (GPNH) and collybistin (ARHGEF9). Recent studies of the Na(+)/Cl(-)-dependent glycine transporters GlyT1 and GlyT2 using mouse knockout models and human genetics have revealed that mutations in GlyT2 are a second major cause of hyperekplexia, while the phenotype of the GlyT1 knockout mouse resembles a devastating neurological disorder known as glycine encephalopathy (OMIM 605899). These findings highlight the importance of these transporters in regulating the levels of synaptic glycine.

Item Type:Article
Additional Information:Full text available electronically from the School of Pharmacy Library.
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:1204
Journal or Publication Title:Frontiers in Molecular Neuroscience
Deposited By:Library Staff
Deposited On:18 Dec 2009 10:17
Last Modified:10 Nov 2011 09:46

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