QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 19, 2005, 25(42):9613-9623; doi:10.1523/JNEUROSCI.1488-05.2005

This Article Full Text Full Text (PDF) An erratum has been published Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Cordero-Erausquin, M. Articles by Koninck, Y. D. Search for Related Content PubMed PubMed Citation Articles by Cordero-Erausquin, M. Articles by Koninck, Y. D.

 Previous Article  |  Next Article 

Cellular/Molecular
Differential Maturation of GABA Action and Anion Reversal Potential in Spinal Lamina I Neurons: Impact of Chloride Extrusion Capacity

Matilde Cordero-Erausquin,¹ Jeffrey A. M. Coull,^1,2 Dominic Boudreau,¹ Matthias Rolland,¹ and Yves De Koninck^1,2

¹Division de Neurobiologie Cellulaire, Centre de Recherche Université Laval Robert-Giffard, Québec, Québec, Canada G1J 2G3, and ²Department of Pharmacology and Therapeutics, McGill University, Montreal, Québec, Canada H3A 1Y6

A deficit in inhibition in the spinal dorsal horn has been proposed to be an underlying cause of the exaggerated cutaneous sensory reflexes observed in newborn rats. However, the developmental shift in transmembrane anion gradient, potentially affecting the outcome of GABA_A transmission, was shown to be completed within 1 week after birth in the spinal cord, an apparent disparity with the observation that reflex hypersensitivity persists throughout the first 2-3 postnatal weeks.

To further investigate this issue, we used several approaches to assess the action of GABA throughout development in spinal lamina I (LI) neurons. GABA induced an entry of extracellular calcium in LI neurons from postnatal day 0 (P0) to P21 rats, which involved T- and N-type voltage-gated calcium channels. Gramicidin perforated-patch recordings revealed that the shift in anion gradient was completed by P7 in LI neurons. However, high chloride pipette recordings demonstrated that these neurons had not reached their adult chloride extrusion capacity by P10-P11. Simultaneous patch-clamp recordings and calcium imaging revealed that biphasic responses to GABA, consisting of a primary hyperpolarization followed by a rebound depolarization, produced a rise in [Ca²⁺]_i. Thus, even if E_anion predicts GABA_A-induced hyperpolarization from rest, a low chloride extrusion capacity can cause a rebound depolarization and an ensuing rise in [Ca²⁺]_i.

We demonstrate that GABA action in LI neurons matures throughout the first 3 postnatal weeks, therefore matching the time course of maturation of withdrawal reflexes. Immature spinal GABA signaling may thus contribute to the nociceptive hypersensitivity in infant rats.

Key words: development; dorsal horn; nociception; pain; inhibition; perforated patch-clamp; calcium channels; chloride; anion transport

---

Received Dec 12, 2004; revised September 5, 2005; accepted September 6, 2005.

This article has been cited by other articles:

				R. A. Ingram, M. Fitzgerald, and M. L. Baccei Developmental Changes in the Fidelity and Short-Term Plasticity of GABAergic Synapses in the Neonatal Rat Dorsal Horn J Neurophysiol, June 1, 2008; 99(6): 3144 - 3150. [Abstract] [Full Text] [PDF]

				A. Delpy, A.-E. Allain, P. Meyrand, and P. Branchereau NKCC1 cotransporter inactivation underlies embryonic development of chloride-mediated inhibition in mouse spinal motoneuron J. Physiol., February 15, 2008; 586(4): 1059 - 1075. [Abstract] [Full Text] [PDF]

				I. Milenkovic, M. Witte, R. Turecek, M. Heinrich, T. Reinert, and R. Rubsamen Development of Chloride-Mediated Inhibition in Neurons of the Anteroventral Cochlear Nucleus of Gerbil (Meriones unguiculatus) J Neurophysiol, September 1, 2007; 98(3): 1634 - 1644. [Abstract] [Full Text] [PDF]

				L. Bremner, M. Fitzgerald, and M. Baccei Functional GABAA-Receptor-Mediated Inhibition in the Neonatal Dorsal Horn J Neurophysiol, June 1, 2006; 95(6): 3893 - 3897. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help