Open AccessTo Depolarize or Hyperpolarize? At the Axon Initial Segment, E GABA Sets the Stage
Author(s) -
Stafstrom Carl E.
Publication year - 2009
Publication title -
epilepsy currents
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.415
H-Index - 22
eISSN - 1535-7511
pISSN - 1535-7597
DOI - 10.1111/j.1535-7511.2008.01281.x
Subject(s) - depolarization , inhibitory postsynaptic potential , excitatory postsynaptic potential , neuroscience , cotransporter , axon , gabaergic , postsynaptic potential , biophysics , soma , gabaa receptor , chemistry , postsynaptic current , reversal potential , biology , electrophysiology , receptor , biochemistry , patch clamp , sodium , organic chemistry
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.