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Author Notes:

Address for reprint requests and other correspondence: P. Wenner, Department of Physiology, Room 601, Whitehead Building, Emory University School of Medicine, Atlanta, GA 30322; Email: pwenner@emory.edu

We thank Dr. Martin Pinter for helpful discussions.

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Research Funding:

This research was supported by National Institute of Neurological Disorders and Stroke (NINDS) Grant NS-046510 and National Science Foundation Grant 0616097 to P. Wenner and by the intramural program of the NINDS.

NKCC1 and AE3 Appear to Accumulate Chloride in Embryonic Motoneurons

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Journal Title:

Journal of Neurophysiology

Volume:

Volume 101, Number 2

Publisher:

, Pages 507-518

Type of Work:

Article | Post-print: After Peer Review

Abstract:

During early development, γ-aminobutyric acid (GABA) depolarizes and excites neurons, contrary to its typical function in the mature nervous system. As a result, developing networks are hyperexcitable and experience a spontaneous network activity that is important for several aspects of development. GABA is depolarizing because chloride is accumulated beyond its passive distribution in these developing cells. Identifying all of the transporters that accumulate chloride in immature neurons has been elusive and it is unknown whether chloride levels are different at synaptic and extrasynaptic locations. We have therefore assessed intracellular chloride levels specifically at synaptic locations in embryonic motoneurons by measuring the GABAergic reversal potential (EGABA) for GABAA miniature postsynaptic currents. When whole cell patch solutions contained 17–52 mM chloride, we found that synaptic EGABA was around −30 mV. Because of the low HCO3− permeability of the GABAA receptor, this value of EGABA corresponds to approximately 50 mM intracellular chloride. It is likely that synaptic chloride is maintained at levels higher than the patch solution by chloride accumulators. We show that the Na+-K+-2Cl− cotransporter, NKCC1, is clearly involved in the accumulation of chloride in motoneurons because blocking this transporter hyperpolarized EGABA and reduced nerve potentials evoked by local application of a GABAA agonist. However, chloride accumulation following NKCC1 block was still clearly present. We find physiological evidence of chloride accumulation that is dependent on HCO3− and sensitive to an anion exchanger blocker. These results suggest that the anion exchanger, AE3, is also likely to contribute to chloride accumulation in embryonic motoneurons.

Copyright information:

© 2009, American Physiological Society

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