Abstract
AbstractGABA, a major inhibitory neurotransmitter in the adult CNS, is excitatory at early developmental stages as a result of the elevated intracellular Cl– concentration ([Cl–]i). This functional switch is primarily attributable to the K+‐Cl– co‐transporter KCC2, the expression of which is developmentally regulated in neurons. Previously, we reported that KCC2 interacts with brain‐type creatine kinase (CKB). To elucidate the functional significance of this interaction, HEK293 cells were transfected with KCC2 and glycine receptor α2 subunit, and gramicidin‐perforated patch‐clamp recordings were performed to measure the glycine reversal potential (Egly), giving an estimate of [Cl–]i. KCC2‐expressing cells displayed the expected changes in Egly following alterations in the extracellular K+ concentration ([K+]o) or administration of an inhibitor of KCCs, suggesting that the KCC2 function was being properly assessed. When added into KCC2‐expressing cells, dominant‐negative CKB induced a depolarizing shift in Egly and reduced the hyperpolarizing shift in Egly seen in response to a lowering of [K+]o compared with wild‐type CKB. Moreover, 2,4‐dinitrofluorobenzene (DNFB), an inhibitor of CKs, shifted Egly in the depolarizing direction. In primary cortical neurons expressing CKB, the GABA reversal potential was also shifted in the depolarizing direction by DNFB. Our findings suggest that, in the cellular micro‐environment, CKB activates the KCC2 function.
References
51
Referenced
61
10.1016/0014-5793(91)80383-E
10.1046/j.1471-4159.2000.0742520.x
10.1016/0014-5793(83)80394-9
10.1038/nrn920
10.1002/j.1460-2075.1993.tb06050.x
10.1080/15622970310029916
10.1085/jgp.100.1.1
10.1152/ajpcell.1995.268.3.C660
10.1038/nature01868
10.1096/fj.01-0466fje
10.1016/S0169-328X(97)00343-4
10.1523/JNEUROSCI.20-21-08069.2000
/ J. Neurosci. / Potassium‐coupled chloride co‐transporter controls intracellular chloride in rat neocortical pyramidal neurons by DeFazio R. A. (2000)10.1146/annurev.physiol.64.081501.155847
10.1016/S0304-4165(99)00113-0
10.1113/jphysiol.1995.sp020649
10.1002/cne.903430311
10.1016/S0092-8674(01)00341-5
10.1152/ajpcell.1999.276.2.C328
10.1016/S0021-9258(18)52891-X
/ J. Biol. Chem. / A Na+‐dependent creatine transporter in rabbit brain, muscle, heart, and kidney: cDNA cloning and functional expression by Guimbal C. (1993)10.1016/0167-4838(95)00083-7
10.1016/0896-6273(89)90258-4
10.1523/JNEUROSCI.2909-04.2004
10.1016/S0014-5793(04)00328-X
10.1016/j.bbrc.2004.12.010
10.1152/jn.00142.2003
10.1523/JNEUROSCI.19-12-04695.1999
/ J. Neurosci. / A furosemide‐sensitive K+‐Cl– co‐transporter counteracts intracellular Cl– accumulation and depletion in cultured rat midbrain neurons by Jarolimek W. (1999)10.1046/j.1460-9568.2002.02001.x
10.1523/JNEUROSCI.21-21-08339.2001
10.1016/S0165-6147(02)02138-7
{'key': 'e_1_2_7_31_1', 'first-page': '3172', 'article-title': 'Cyclocreatine (1‐carboxymethyl‐2‐iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors', 'volume': '53', 'author': 'Lillie J. W.', 'year': '1993', 'journal-title': 'Cancer Res.'}
/ Cancer Res. / Cyclocreatine (1‐carboxymethyl‐2‐iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors by Lillie J. W. (1993)10.1016/0167-4838(94)90077-9
10.1002/(SICI)1097-4695(19990615)39:4<558::AID-NEU9>3.0.CO;2-5
10.1073/pnas.97.22.12062
10.1016/S0958-1669(99)00010-5
10.1242/jeb.201.14.2091
/ J. Exp. Biol. / The electroneutral cation–chloride co‐transporters by Mount D. B. (1998)10.1097/01.WCB.0000033966.83623.7D
10.1038/nrn919
10.1152/ajpcell.1997.273.5.C1516
10.1074/jbc.271.27.16245
/ J. Biol. Chem. / Molecular characterization of a putative K‐Cl co‐transporter in rat brain by Payne J. A. (1996)10.1016/S0166-2236(03)00068-7
/ Trends Neurosci. / Cation–chloride co‐transporters in neuronal communication, development and trauma by Payne J. A. (2003)10.1002/j.1460-2075.1992.tb05529.x
10.1038/16697
10.1007/BF00307817
10.1073/pnas.88.23.10540
10.1016/S0092-8674(00)80186-5
10.1152/ajpcell.2000.279.3.C860
10.1523/JNEUROSCI.20-20-07531.2000
/ J. Neurosci. / Abnormal GABAA receptor‐mediated currents in dorsal root ganglion neurons isolated from Na‐K‐2Cl co‐transporter null mice by Sung K.‐W. (2000)10.1016/0092-8674(85)90085-6
10.1152/jn.00721.2002
10.1152/physrev.2000.80.3.1107
10.1113/jphysiol.2004.062471
/ J. Physiol. (Lond.) / Cl– uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1 by Yamada J. (2004)
Dates
Type | When |
---|---|
Created | 19 years, 9 months ago (Nov. 29, 2005, 6:14 a.m.) |
Deposited | 1 year, 10 months ago (Oct. 14, 2023, 10:46 p.m.) |
Indexed | 11 months, 2 weeks ago (Sept. 13, 2024, 9:51 p.m.) |
Issued | 19 years, 9 months ago (Nov. 29, 2005) |
Published | 19 years, 9 months ago (Nov. 29, 2005) |
Published Online | 19 years, 9 months ago (Nov. 29, 2005) |
Published Print | 19 years, 7 months ago (Jan. 1, 2006) |
@article{Inoue_2005, title={Brain‐type creatine kinase activates neuron‐specific K+‐Cl– co‐transporter KCC2}, volume={96}, ISSN={1471-4159}, url={http://dx.doi.org/10.1111/j.1471-4159.2005.03560.x}, DOI={10.1111/j.1471-4159.2005.03560.x}, number={2}, journal={Journal of Neurochemistry}, publisher={Wiley}, author={Inoue, Koichi and Yamada, Junko and Ueno, Shinya and Fukuda, Atsuo}, year={2005}, month=nov, pages={598–608} }