BERGMANN GLIAL GlyT1 MEDIATES GLYCINE UPTAKE AND RELEASE IN MOUSE CEREBELLAR SLICES
Abstract number :
1.083
Submission category :
Year :
2003
Submission ID :
567
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Angelique Bordey, Hao Huang, Latifa Barakat, Dennis Spencer Department of Neurosurgery, Yale University School of Medicine, New Haven, CT
Glycine is an inhibitory neurotransmitter and is critical for NMDA receptor activation. These roles are dependent on extracellular glycine levels, which are regulated by Na+/Cl--dependent glycine transporters (GlyTs) in neurons and glia. In particular, the glial GlyT subtype GlyT1 is well located to activate NMDA receptors. However, glial GlyTs have not been studied in an intact system thus far.
Whole-cell patch-clamp recordings were obtained from Bergmann glia in mice cerebellar slices to determine whether these glia express functional GlyT1 that can mediate both glycine uptake and efflux.
In the presence of a glycine receptor blocker glycine induced inward currents that were abolished by external Na+ removal, identifying them as transport currents. Glycine transport currents were markedly diminished by external Cl- reduction and were inwardly rectifying between -70 and +50 mV. Sarcosine, a selective competitive inhibitor of GlyT1, reduced glycine transport currents by 87% while competitive blockers of Na+-dependent glycine transporters, systems A and ASC did not affect glycine transport currents. Sarcosine also acted as a substrate for GlyTs and induced Na+- and voltage-dependent inward currents. Following internal glycine perfusion during the recording, an outward current progressively developed at -50 mV and reduced external glycine-induced uptake currents. These outward currents activated above -60 mV and increased with more depolarized potentials.
Overall, these results demonstrate for the first time that Bergmann glia express functional GlyT1 that can work in reverse at near-physiological ionic and internal glycine conditions in brain slices. These glial GlyTs can likely mediate glycine efflux under conditions of metabolic impairments like epilesy.
[Supported by: NIH R01NS/HD42189-01A2 and the American Epilepsy Society.]