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The Journal of Neuroscience, November 1, 2000, 20(21):8069-8076
Potassium-Coupled Chloride Cotransport Controls Intracellular
Chloride in Rat Neocortical Pyramidal Neurons
R. Anthony
DeFazio,
Sotirios
Keros,
Michael W.
Quick, and
John J.
Hablitz
Department of Neurobiology, University of Alabama at Birmingham,
Birmingham, Alabama 35294
Chloride (Cl ) homeostasis is critical
for many cell functions including cell signaling and volume regulation.
The action of GABA at GABAA receptors is primarily
determined by the concentration of intracellular
Cl. Developmental regulation of intracellular
Cl results in a depolarizing response to GABA in
immature neocortical neurons and a hyperpolarizing or shunting response
in mature neocortical neurons. One protein that participates in
Cl homeostasis is the neuron-specific
K+-Cl cotransporter (KCC2).
Thermodynamic considerations predict that in the physiological ranges
of intracellular Cl and extracellular
K+ concentrations, KCC2 can act to either extrude or
accumulate Cl. To test this hypothesis, we
examined KCC2 function in pyramidal cells from rat neocortical slices
in mature (18-28 d postnatal) and immature (3-6 d postnatal) rats.
Intracellular Cl concentration was estimated from
the reversal potential of whole-cell currents evoked by local
application of exogenous GABA. Both increasing and decreasing the
extracellular K+ concentration resulted in a
concomitant change in intracellular Cl
concentration in neurons from mature rats. KCC2 inhibition by furosemide caused a change in the intracellular Cl
concentration that depended on the concentration of pipette
Cl; in recordings with low pipette
Cl, furosemide lowered intracellular
Cl, whereas in recordings with elevated pipette
Cl, furosemide raised intracellular
Cl. In neurons from neonatal rats, manipulation of
extracellular K+ had no effect on intracellular
Cl concentration, consistent with the minimal KCC2
mRNA levels observed in neocortical neurons from immature animals.
These data demonstrate a physiologically relevant and developmentally
regulated role for KCC2 in Cl homeostasis via both
Cl extrusion and accumulation.
Key words:
potassium chloride cotransporter; GABA receptors; KCC2; development; chloride homeostasis; rt-PCR
Copyright © 2000 Society for Neuroscience 0270-6474/00/20218069-08$05.00/0
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|
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|
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|
|
|
|
|
|
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|
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|
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[Full Text]
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|
|
|
|
|
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95(3):
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|
|
|
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|
|
|
|
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|
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|
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[Full Text]
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|
|
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|
|
|
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94(3):
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[Full Text]
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|
|
|
|
|
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93(4):
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
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562(1):
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[Abstract]
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|
|
|
|
|
|
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287(4):
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[Abstract]
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|
|
|
|
|
|
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19(1):
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[Abstract]
[Full Text]
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|
|
|
|
|
|
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J. Physiol.,
June 15, 2004;
557(3):
829 - 841.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Rivera, J. Voipio, J. Thomas-Crusells, H. Li, Z. Emri, S. Sipila, J. A. Payne, L. Minichiello, M. Saarma, and K. Kaila
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J. Neurosci.,
May 12, 2004;
24(19):
4683 - 4691.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Galeffi, R. Sah, B. B. Pond, A. George, and R. D. Schwartz-Bloom
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J. Neurosci.,
May 5, 2004;
24(18):
4478 - 4488.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Meeks and S. Mennerick
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J. Neurosci.,
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24(1):
197 - 206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Wardle and M.-m. Poo
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J. Neurosci.,
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23(25):
8722 - 8732.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Gulacsi, C. R. Lee, A. Sik, T. Viitanen, K. Kaila, J. M. Tepper, and T. F. Freund
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September 10, 2003;
23(23):
8237 - 8246.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Vale, J. Schoorlemmer, and D. H. Sanes
Deafness Disrupts Chloride Transporter Function and Inhibitory Synaptic Transmission
J. Neurosci.,
August 20, 2003;
23(20):
7516 - 7524.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. L. Thio, A. Shanmugam, K. Isenberg, and K. Yamada
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J Neurophysiol,
July 1, 2003;
90(1):
89 - 99.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Leupen, S. A. Tobet, W. F. Crowley Jr., and K. Kaila
Heterogeneous Expression of the Potassium-Chloride Cotransporter KCC2 in Gonadotropin-Releasing Hormone Neurons of the Adult Mouse
Endocrinology,
July 1, 2003;
144(7):
3031 - 3036.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Balakrishnan, M. Becker, S. Lohrke, H. G. Nothwang, E. Guresir, and E. Friauf
Expression and Function of Chloride Transporters during Development of Inhibitory Neurotransmission in the Auditory Brainstem
J. Neurosci.,
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23(10):
4134 - 4145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Toyoda, K. Ohno, J. Yamada, M. Ikeda, A. Okabe, K. Sato, K. Hashimoto, and A. Fukuda
Induction of NMDA and GABAA Receptor-Mediated Ca2+ Oscillations With KCC2 mRNA Downregulation in Injured Facial Motoneurons
J Neurophysiol,
March 1, 2003;
89(3):
1353 - 1362.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. Schomberg, J. Bauer, D. B. Kintner, G. Su, A. Flemmer, B. Forbush, and D. Sun
Cross Talk Between the GABAA Receptor and the Na-K-Cl Cotransporter Is Mediated by Intracellular Cl-
J Neurophysiol,
January 1, 2003;
89(1):
159 - 167.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Rivera, H. Li, J. Thomas-Crusells, H. Lahtinen, T. Viitanen, A. Nanobashvili, Z. Kokaia, M. S. Airaksinen, J. Voipio, K. Kaila, et al.
BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion
J. Cell Biol.,
December 9, 2002;
159(5):
747 - 752.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. DeFazio, S. Heger, S. R. Ojeda, and S. M. Moenter
Activation of A-Type {gamma}-Aminobutyric Acid Receptors Excites Gonadotropin-Releasing Hormone Neurons
Mol. Endocrinol.,
December 1, 2002;
16(12):
2872 - 2891.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Billups and D. Attwell
Control of intracellular chloride concentration and GABA response polarity in rat retinal ON bipolar cells
J. Physiol.,
November 15, 2002;
545(1):
183 - 198.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. C. Chattipakorn and L. L. McMahon
Pharmacological Characterization of Glycine-Gated Chloride Currents Recorded in Rat Hippocampal Slices
J Neurophysiol,
March 1, 2002;
87(3):
1515 - 1525.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Kelsch, S. Hormuzdi, E. Straube, A. Lewen, H. Monyer, and U. Misgeld
Insulin-Like Growth Factor 1 and a Cytosolic Tyrosine Kinase Activate Chloride Outward Transport during Maturation of Hippocampal Neurons
J. Neurosci.,
November 1, 2001;
21(21):
8339 - 8347.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Neunlist, K. Michel, D. Reiche, G. Dobreva, K. Huber, and M. Schemann
Glycine activates myenteric neurones in adult guinea-pigs
J. Physiol.,
November 1, 2001;
536(3):
727 - 739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. F M Van Brederode, T. Takigawa, and C. Alzheimer
GABA-evoked chloride currents do not differ between dendrites and somata of rat neocortical neurons
J. Physiol.,
June 15, 2001;
533(3):
711 - 716.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
