1. GABAergic Depolarization of the Axon Initial Segment in Cortical Principal Neurons Is Caused by the Na–K–2Cl Cotransporter NKCC1
- Author
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Junko Yamada, Leonard Khiroug, Ramil Afzalov, Kai Kaila, Stanislav Khirug, and Juha Voipio
- Subjects
Patch-Clamp Techniques ,Sodium-Potassium-Chloride Symporters ,Green Fluorescent Proteins ,Mice, Transgenic ,Inhibitory postsynaptic potential ,Statistics, Nonparametric ,gamma-Aminobutyric acid ,Membrane Potentials ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Sodium Potassium Chloride Symporter Inhibitors ,Basic Science ,Postsynaptic potential ,medicine ,Animals ,Solute Carrier Family 12, Member 2 ,Bumetanide ,gamma-Aminobutyric Acid ,Phenylacetates ,030304 developmental biology ,Cerebral Cortex ,Neurons ,Membrane potential ,0303 health sciences ,Photolysis ,Chemistry ,General Neuroscience ,Neural Inhibition ,Axon initial segment ,Axons ,nervous system ,Excitatory postsynaptic potential ,GABAergic ,Cotransporter ,Brief Communications ,Neuroscience ,030217 neurology & neurosurgery ,medicine.drug - 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 (EGABA) of GABAAreceptor-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 theEGABAvalues from the AIS to the soma and dendrites become progressively more negative. Data fromNKCC1−/−and bumetanide-exposed neurons indicated that the depolarizingEGABAat 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.
- Published
- 2008