Induction of NMDA and GABA<sub>A</sub>Receptor-Mediated Ca<sup>2+</sup>Oscillations With KCC2 mRNA Downregulation in Injured Facial Motoneurons

Journal of Neurophysiology - Tập 89 Số 3 - Trang 1353-1362 - 2003
Hiroki Toyoda1,2, Koji Ohno3, Junko Yamada4, Masahiko Ikeda1, Akihito Okabe1, Kohji Sato3, Kenji Hashimoto2, Atsuo Fukuda4,1
1Departments of Physiology
2Oral and Maxillofacial Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192; and
3Anatomy and
4Department of Biological Information Processing, Graduate School of Electronic Science and Technology, Shizuoka University, Hamamatsu, Shizuoka 432-8011, Japan

Tóm tắt

To clarify the changes that occur in γ-aminobutyric acid type A (GABAA) receptor-mediated effects and contribute to alterations in the network activities after neuronal injury, we studied intracellular Ca2+concentration ([Ca2+]i) dynamics in a rat facial-nerve-transection model. In facial motoneurons, an elevation of the resting [Ca2+]i, GABA-mediated [Ca2+]itransients, enhancement of the glutamate-evoked [Ca2+]iincreases, and spontaneous [Ca2+]ioscillations were induced by axotomy. All these axotomy-induced modifications were abolished by the GABAA-receptor antagonist bicuculline and N-methyl-d-aspartate (NMDA)-receptor antagonistd(−)-2-amino-5-phosphonopentanoic acid. A downregulation of K+-Cl−cotransporter (KCC2) mRNA, an increase in intracellular Cl−concentration ([Cl−]i), and transformation of GABAergic hyperpolarization to depolarization were also induced by axotomy. We suggest that in axotomized neurons KCC2 downregulation impairs Cl−homeostasis and makes GABA act depolarizing, resulting in endogenous GABA inducing [Ca2+]ioscillations via facilitation of NMDA-receptor activation. Such GABAA-receptor-mediated [Ca2+]ioscillations may play a role in neural survival and regeneration.

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Journal of Neurophysiology

Tập 89 Số 3

1353-1362

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