Induction of NMDA and GABAA Receptor-Mediated Ca2+ Oscillations With KCC2 mRNA Downregulation in Injured Facial Motoneurons

• Published in: Journal of neurophysiology Vol. 89; no. 3; pp. 1353 - 1362
• Main Authors: Toyoda, Hiroki, Ohno, Koji, Yamada, Junko, Ikeda, Masahiko, Okabe, Akihito, Sato, Kohji, Hashimoto, Kenji, Fukuda, Atsuo
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01.03.2003
• Subjects: Animals; Axotomy; Calcium - metabolism; Calcium Signaling - drug effects; Calcium Signaling - physiology; Chlorides - metabolism; Down-Regulation - physiology; Facial Nerve - cytology; Facial Nerve - physiology; Facial Nerve Injuries - physiopathology; gamma-Aminobutyric Acid - pharmacology; Gene Expression - physiology; Glutamic Acid - pharmacology; K Cl- Cotransporters; Male; Motor Neurons - physiology; Organ Culture Techniques; Rats; Rats, Wistar; Receptors, GABA-A - physiology; Receptors, N-Methyl-D-Aspartate - physiology; RNA, Messenger - metabolism; Symporters - genetics; Symporters - metabolism
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00721.2002

Departments of   1 Physiology,   2 Anatomy, and   3 Oral and Maxillofacial Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192; and   4 Department of Biological Information Processing, Graduate School of Electronic Science and Technology, Shizuoka University, Hamamatsu, Shizuoka 432-8011, Japan Toyoda, Hiroki, Koji Ohno, Junko Yamada, Masahiko Ikeda, Akihito Okabe, Kohji Sato, Kenji Hashimoto, and Atsuo Fukuda. Induction of NMDA and GABA A Receptor-Mediated Ca 2+ Oscillations With KCC2 mRNA Downregulation in Injured Facial Motoneurons. J. Neurophysiol. 89: 1353-1362, 2003. To clarify the changes that occur in -aminobutyric acid type A (GABA A ) receptor-mediated effects and contribute to alterations in the network activities after neuronal injury, we studied intracellular Ca 2+ concentration ([Ca 2+ ] i ) dynamics in a rat facial-nerve-transection model. In facial motoneurons, an elevation of the resting [Ca 2+ ] i , GABA-mediated [Ca 2+ ] i transients, enhancement of the glutamate-evoked [Ca 2+ ] i increases, and spontaneous [Ca 2+ ] i oscillations were induced by axotomy. All these axotomy-induced modifications were abolished by the GABA A -receptor antagonist bicuculline and N -methyl- D -aspartate (NMDA)-receptor antagonist D ( )-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 [Ca 2+ ] i oscillations via facilitation of NMDA-receptor activation. Such GABA A -receptor-mediated [Ca 2+ ] i oscillations may play a role in neural survival and regeneration.