Related Experiment Video
Updated: Jun 28, 2026
Whole-cell Currents Induced by Puff Application of GABA in Brain Slices
Published on: October 12, 2017
A critical role for glycine transporters in hyperexcitability disorders
Robert J Harvey1, Eloisa Carta, Brian R Pearce
1Department of Pharmacology, The School of Pharmacy London, UK.
Insights
Defects in glycine neurotransmission cause hyperekplexia, a motor disorder in newborns. Mutations in glycine receptor genes and glycine transporters like GlyT2 are key causes.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Glycinergic neurotransmission is crucial for motor control.
- Defects in this system lead to hyperekplexia, a neonatal motor disorder.
- Hyperekplexia involves neonatal hypertonia and exaggerated startle reflexes.
Purpose of the Study:
- To investigate the genetic causes of hyperekplexia.
- To identify the roles of glycine receptors and transporters in this disorder.
Main Methods:
- Analysis of mutations in glycine receptor subunit genes (GLRA1, GLRB).
- Investigation of genes encoding glycine receptor-associated proteins (GPNH, ARHGEF9).
- Studies on Na(+)/Cl(-)-dependent glycine transporters (GlyT1, GlyT2) using mouse models and human genetics.
Main Results:
- Mutations in GLRA1 are the primary cause of hyperekplexia.
- Rare mutations in GLRB, GPNH, and ARHGEF9 are also implicated.
- Mutations in GlyT2 represent a second major cause of hyperekplexia.
- GlyT1 transporter dysfunction in mice mimics glycine encephalopathy.
Conclusions:
- Genetic defects in glycine receptors and transporters are central to hyperekplexia.
- Glycine transporters play a vital role in regulating synaptic glycine levels.
- Understanding these genetic underpinnings is critical for diagnosing and potentially treating these neurological disorders.
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.
More Related Videos
Related Concept Videos
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
01:18Antiepileptic Drugs: GABAergic Pathway Potentiators
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for their...
01:14Antiepileptic Drugs: Glutamate Antagonists
01:29Excitatory and Inhibitory Effects of Neurotransmitters
01:19Ligand-gated Ion Channels
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
01:23Role of Neurotransmitters in Memory
Glutamate and Synaptic Plasticity
Glutamate, the brain's main excitatory neurotransmitter, is critical for...