Role for GABA and Glu Plasma Membrane Transporters in the Interplay of Inhibitory and Excitatory Neurotransmission

Héja, László; Karacs, Kinga; Kardos, Julianna

doi:10.2174/156802606777323656

Cited by 19 publications

(9 citation statements)

References 54 publications

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“…As expected [46], [47], the elevated [Glu] o increased neuronal activity resulting in PS amplitude enhancement, most likely arising from intensified neuronal firing rate [48]. Concurrently, blockade of astroglial Glu uptake decreased summa IOS amplitude indicating that Glu robustly taken up by the astroglial EAAT2 [79] also shapes the in vitro apparent IOS. The decrease of summa IOS amplitude can be explained by the blockade of Glu uptake mediated astrocytic cell swelling [25], [26].…”

Section: Discussionsupporting

confidence: 65%

Neuronal and Astroglial Correlates Underlying Spatiotemporal Intrinsic Optical Signal in the Rat Hippocampal Slice

et al. 2013

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Widely used for mapping afferent activated brain areas in vivo, the label-free intrinsic optical signal (IOS) is mainly ascribed to blood volume changes subsequent to glial glutamate uptake. By contrast, IOS imaged in vitro is generally attributed to neuronal and glial cell swelling, however the relative contribution of different cell types and molecular players remained largely unknown. We characterized IOS to Schaffer collateral stimulation in the rat hippocampal slice using a 464-element photodiode-array device that enables IOS monitoring at 0.6 ms time-resolution in combination with simultaneous field potential recordings. We used brief half-maximal stimuli by applying a medium intensity 50 Volt-stimulus train within 50 ms (20 Hz). IOS was primarily observed in the str. pyramidale and proximal region of the str. radiatum of the hippocampus. It was eliminated by tetrodotoxin blockade of voltage-gated Na+ channels and was significantly enhanced by suppressing inhibitory signaling with gamma-aminobutyric acid(A) receptor antagonist picrotoxin. We found that IOS was predominantly initiated by postsynaptic Glu receptor activation and progressed by the activation of astroglial Glu transporters and Mg2+-independent astroglial N-methyl-D-aspartate receptors. Under control conditions, role for neuronal K+/Cl− cotransporter KCC2, but not for glial Na+/K+/Cl− cotransporter NKCC1 was observed. Slight enhancement and inhibition of IOS through non-specific Cl− and volume-regulated anion channels, respectively, were also depicted. High-frequency IOS imaging, evoked by brief afferent stimulation in brain slices provide a new paradigm for studying mechanisms underlying IOS genesis. Major players disclosed this way imply that spatiotemporal IOS reflects glutamatergic neuronal activation and astroglial response, as observed within the hippocampus. Our model may help to better interpret in vivo IOS and support diagnosis in the future.

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Section: Discussionsupporting

confidence: 65%

Neuronal and Astroglial Correlates Underlying Spatiotemporal Intrinsic Optical Signal in the Rat Hippocampal Slice

et al. 2013

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“…To date, five structurally distinct subtypes of mammalian Glu or excitatory amino acid (EAATs) transporters, GLAST (EAAT1), GLT1 (EAAT2), EAAC1 (EAAT3), EAAT4 and EAAT5 (see Heja et al, this issue [75]), and three types of vesicular Glu transporters (VGLUT1-3) have been identified and characterized [63,76,77].…”

Section: Glu Transporters: Release and Uptakementioning

confidence: 99%

Glutamate as a Modulator of Embryonic and Adult Neurogenesis

Schlett

2006

CTMC

114

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It has been widely accepted that neurogenesis continues throughout life. Neural stem cells can be found in the ventricular zone of the embryonic and in restricted regions of the adult central nervous system, including subventricular and subgranular zones of the hippocampal dentate gyrus. The network of signaling mechanisms determining whether neural stem cells remain in a proliferative state or differentiate is only partly discovered. Recent advances indicate that glutamate (Glu), the predominant excitatory neurotransmitter in mature neurons, can influence immature neural cell proliferation and differentiation, as well. Despite many similarities, Glu actions on neurogenesis in the developing and adult brain show distinct differences and are far from being clear. Due to alterations of Glu transport mechanisms, extracellular Glu level is high in the embryonic CNS. Glu acts non-synaptically on dividing progenitors either by directly activating ionotropic and/or metabotropic Glu receptors or can influence other cells which are located in the vicinity of proliferating cells and produce molecules regulating neural precursor cell proliferation by other mechanisms. Due to the complexity of signaling pathways and to regional differences in neural precursors, Glu can influence proliferation and neuronal commitment as well, and acts as a positive regulator of neurogenesis. Brain injuries like ischemia, epilepsy or stress lead to severe neuronal death and additionally, influence neurogenesis, as well. Glu homeostasis is altered under these pathological circumstances, implying that therapeutic treatments mediating Glu signaling might be useful to increase neuronal replacement after cell loss in the brain.

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“…Glutamate is especially an important excitatory neurotransmitter in the brain (Shen et al, 2010;Yang et al, 2011). Its release is the principal pathological mechanism in ischemia brain damage (Dohmen et al, 2005;Heja et al, 2006). Then a cascade of events will lead to cell death (Butcher et al, 1990;Choi et al, 1988;Small and Buchan, 1996).…”

Section: Changes In Amino Acid Contentmentioning

confidence: 99%

Effect of Baicalin-loaded PEGylated cationic solid lipid nanoparticles modified by OX26 antibody on regulating the levels of baicalin and amino acids during cerebral ischemia–reperfusion in rats

Liu

Zhang

et al. 2015

International Journal of Pharmaceutics

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Role for GABA and Glu Plasma Membrane Transporters in the Interplay of Inhibitory and Excitatory Neurotransmission

Cited by 19 publications

References 54 publications

Neuronal and Astroglial Correlates Underlying Spatiotemporal Intrinsic Optical Signal in the Rat Hippocampal Slice

Neuronal and Astroglial Correlates Underlying Spatiotemporal Intrinsic Optical Signal in the Rat Hippocampal Slice

Glutamate as a Modulator of Embryonic and Adult Neurogenesis

Effect of Baicalin-loaded PEGylated cationic solid lipid nanoparticles modified by OX26 antibody on regulating the levels of baicalin and amino acids during cerebral ischemia–reperfusion in rats

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