GABAergic depolarization of the axon initial segment in cortical principal neurons is caused by the Na-K-2Cl cotransporter NKCC1. Export

@article{citeulike:2764317, abstract = {GABAergic terminals of axo-axonic cells (AACs) are exclusively located on the axon initial segment (AIS) of cortical principal neurons, and they are generally thought to exert a powerful inhibitory action. However, recent work (Szabadics et al., 2006) indicates that this input from AACs can be depolarizing and even excitatory. Here, we used local photolysis of caged GABA to measure reversal potentials (E(GABA)) of GABA(A) receptor-mediated currents and to estimate the local chloride concentration in the AIS compared with other cellular compartments in dentate granule cells and neocortical pyramidal neurons. We found a robust axo-somato-dendritic gradient in which the E(GABA) values from the AIS to the soma and dendrites become progressively more negative. Data from NKCC1(-/-) and bumetanide-exposed neurons indicated that the depolarizing E(GABA) at the AIS is set by chloride uptake mediated by the Na-K-2Cl cotransporter NKCC1. Our findings demonstrate that spatially distinct interneuronal inputs can induce postsynaptic voltage responses with different amplitudes and polarities as governed by the subcellular distributions of plasmalemmal chloride transporters.}, address = {Department of Biological and Environmental Sciences, University of Helsinki, FIN-00014 Helsinki, Finland.}, author = {Khirug, S. and Yamada, J. and Afzalov, R. and Voipio, J. and Khiroug, L. and Kaila, K.}, citeulike-article-id = {2764317}, citeulike-linkout-0 = {http://dx.doi.org/10.1523/JNEUROSCI.0908-08.2008}, citeulike-linkout-1 = {http://www.jneurosci.org/cgi/content/abstract/28/18/4635}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18448640}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18448640}, day = {30}, doi = {10.1523/JNEUROSCI.0908-08.2008}, issn = {1529-2401}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, keywords = {ais, axo-axonique, chandelier}, month = {April}, number = {18}, pages = {4635--4639}, posted-at = {2009-05-25 08:34:26}, priority = {2}, title = {GABAergic depolarization of the axon initial segment in cortical principal neurons is caused by the Na-K-2Cl cotransporter NKCC1.}, url = {http://dx.doi.org/10.1523/JNEUROSCI.0908-08.2008}, volume = {28}, year = {2008} }

TY - JOUR ID - citeulike:2764317 L3 - citeulike-article-id:2764317 N2 - GABAergic terminals of axo-axonic cells (AACs) are exclusively located on the axon initial segment (AIS) of cortical principal neurons, and they are generally thought to exert a powerful inhibitory action. However, recent work (Szabadics et al., 2006) indicates that this input from AACs can be depolarizing and even excitatory. Here, we used local photolysis of caged GABA to measure reversal potentials (E(GABA)) of GABA(A) receptor-mediated currents and to estimate the local chloride concentration in the AIS compared with other cellular compartments in dentate granule cells and neocortical pyramidal neurons. We found a robust axo-somato-dendritic gradient in which the E(GABA) values from the AIS to the soma and dendrites become progressively more negative. Data from NKCC1(-/-) and bumetanide-exposed neurons indicated that the depolarizing E(GABA) at the AIS is set by chloride uptake mediated by the Na-K-2Cl cotransporter NKCC1. Our findings demonstrate that spatially distinct interneuronal inputs can induce postsynaptic voltage responses with different amplitudes and polarities as governed by the subcellular distributions of plasmalemmal chloride transporters. IS - 18 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience SN - 1529-2401 AD - Department of Biological and Environmental Sciences, University of Helsinki, FIN-00014 Helsinki, Finland. EP - 4639 TI - GABAergic depolarization of the axon initial segment in cortical principal neurons is caused by the Na-K-2Cl cotransporter NKCC1. VL - 28 SP - 4635 KW - ais KW - axo-axonique KW - chandelier AU - Khirug, S AU - Yamada, J AU - Afzalov, R AU - Voipio, J AU - Khiroug, L AU - Kaila, K PY - 2008/04/30/ UR - http://dx.doi.org/10.1523/JNEUROSCI.0908-08.2008 ER -