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Astrocytic glutamate release-induced transient depolarization and epileptiform discharges in hippocampal CA1 pyramidal neurons.
J Neurophysiol 2005; 94(6):4121-30JN

Abstract

A paroxysmal depolarization shift (PDS) has been suggested to be a hallmark for epileptic activity in partial-onset seizures. By monitoring membrane potentials and currents in pairs of pyramidal neurons and astrocytes with dual patch-clamp recording and exocytosis of vesicles from astrocytes with two-photon laser scanning microscopy in hippocampal slices, we found that infusion of inositol 1,4,5-trisphosphate (IP(3)) into astrocytes by patch pipettes induced astrocytic glutamate release that triggered a transient depolarization (TD) and epileptiform discharges in CA1 pyramidal neurons. The TD is due to a tetrodotoxin (TTX)-insensitive slowly decaying transient inward current (STC). Astrocytic glutamate release simultaneously triggers both the STC in pyramidal neurons and a transport current (TC) in astrocytes. The neuronal STC is mediated by ionotropic glutamate receptors leading to the TD and epileptiform discharges; while the astrocytic TC is a glutamate reuptake current resulting from transporting released glutamate into the patched astrocyte. Fusion of a large vesicle in astrocytes was immediately followed by an astrocytic TC, suggesting that the fused vesicle contains glutamate. Both fusion of large vesicles and astrocytic TCs were blocked by tetanus toxin (TeNT), suggesting that astrocytic glutamate release is via SNARE-dependent exocytosis of glutamate-containing vesicles. In the presence of TTX, the epileptogenic reagent, 4-AP, also induced similar neuronal STCs and astrocytic TCs, suggesting that astrocytic glutamate release may play an epileptogenic role in initiation of epileptic seizures under pathological conditions. Our study provides a novel mechanism, astrocytic release of glutamate, for seizure initiation.

Authors+Show Affiliations

Department. of Cell Biology and Anatomy, New York Medical College, Valhalla, 10595, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16162834

Citation

Kang, Ning, et al. "Astrocytic Glutamate Release-induced Transient Depolarization and Epileptiform Discharges in Hippocampal CA1 Pyramidal Neurons." Journal of Neurophysiology, vol. 94, no. 6, 2005, pp. 4121-30.
Kang N, Xu J, Xu Q, et al. Astrocytic glutamate release-induced transient depolarization and epileptiform discharges in hippocampal CA1 pyramidal neurons. J Neurophysiol. 2005;94(6):4121-30.
Kang, N., Xu, J., Xu, Q., Nedergaard, M., & Kang, J. (2005). Astrocytic glutamate release-induced transient depolarization and epileptiform discharges in hippocampal CA1 pyramidal neurons. Journal of Neurophysiology, 94(6), pp. 4121-30.
Kang N, et al. Astrocytic Glutamate Release-induced Transient Depolarization and Epileptiform Discharges in Hippocampal CA1 Pyramidal Neurons. J Neurophysiol. 2005;94(6):4121-30. PubMed PMID: 16162834.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Astrocytic glutamate release-induced transient depolarization and epileptiform discharges in hippocampal CA1 pyramidal neurons. AU - Kang,Ning, AU - Xu,Jun, AU - Xu,Qiwu, AU - Nedergaard,Maiken, AU - Kang,Jian, Y1 - 2005/09/14/ PY - 2005/9/16/pubmed PY - 2006/1/26/medline PY - 2005/9/16/entrez SP - 4121 EP - 30 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 94 IS - 6 N2 - A paroxysmal depolarization shift (PDS) has been suggested to be a hallmark for epileptic activity in partial-onset seizures. By monitoring membrane potentials and currents in pairs of pyramidal neurons and astrocytes with dual patch-clamp recording and exocytosis of vesicles from astrocytes with two-photon laser scanning microscopy in hippocampal slices, we found that infusion of inositol 1,4,5-trisphosphate (IP(3)) into astrocytes by patch pipettes induced astrocytic glutamate release that triggered a transient depolarization (TD) and epileptiform discharges in CA1 pyramidal neurons. The TD is due to a tetrodotoxin (TTX)-insensitive slowly decaying transient inward current (STC). Astrocytic glutamate release simultaneously triggers both the STC in pyramidal neurons and a transport current (TC) in astrocytes. The neuronal STC is mediated by ionotropic glutamate receptors leading to the TD and epileptiform discharges; while the astrocytic TC is a glutamate reuptake current resulting from transporting released glutamate into the patched astrocyte. Fusion of a large vesicle in astrocytes was immediately followed by an astrocytic TC, suggesting that the fused vesicle contains glutamate. Both fusion of large vesicles and astrocytic TCs were blocked by tetanus toxin (TeNT), suggesting that astrocytic glutamate release is via SNARE-dependent exocytosis of glutamate-containing vesicles. In the presence of TTX, the epileptogenic reagent, 4-AP, also induced similar neuronal STCs and astrocytic TCs, suggesting that astrocytic glutamate release may play an epileptogenic role in initiation of epileptic seizures under pathological conditions. Our study provides a novel mechanism, astrocytic release of glutamate, for seizure initiation. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/16162834/Astrocytic_glutamate_release_induced_transient_depolarization_and_epileptiform_discharges_in_hippocampal_CA1_pyramidal_neurons_ L2 - http://www.physiology.org/doi/full/10.1152/jn.00448.2005?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -