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Role of Na‐K‐2Cl symporter in GABA‐evoked excitation in rat enteric neurons
Author(s) -
Liu Sumei,
Ji Tuo,
Ren Wei,
Qu MeiHua,
Zhu JinXia,
Wood Jackie D
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1160.5
Subject(s) - depolarization , reversal potential , cotransporter , myenteric plexus , excitatory postsynaptic potential , symporter , membrane potential , enteric nervous system , electrophysiology , chemistry , bumetanide , gabaa receptor , niflumic acid , medicine , intracellular , endocrinology , gamma aminobutyric acid , gabaergic , neuroscience , biophysics , receptor , biology , patch clamp , biochemistry , transporter , immunohistochemistry , sodium , organic chemistry , gene
Background and Aims Gamma‐aminobutyric acid (GABA) inhibits neurons in the brain and spinal cord. GABA does the opposite in neurons of the enteric nervous system (ENS) where its mechanism of excitation is unclear. We aimed to test a hypothesis that the Na + ‐K + ‐2Cl − symporter (NKCC) maintains high intracellular Cl − and contributes to GABA excitation in ENS neurons. Methods Intracellular electrophysiological recording was used to record GABA‐evoked responses in the myenteric plexus of the rat colon. Immunofluorescence and Western blot analysis were used to study the expression of NKCC. Results Both NKCC1 and NKCC2 proteins were expressed in ENS neurons in postnatal and adult rats. NKCC1 and NKCC2 were coexpressed with the GABA A receptor. The K + ‐Cl − cotransporter 2 (KCC2), a Cl − extruder, was not expressed. GABA depolarized the membrane potential in ENS neurons with a reversed potential of −20 mV, which is near the Cl − equilibrium potential. Blockade of NKCC by bumetanide or furosemide suppressed GABA‐evoked depolarization and shifted the reversal potential in the hyperpolarizing direction. Neither the KCC blocker nor the Cl − /HCO 3 − exchange inhibitor suppressed GABA‐evoked depolarization. Conclusions NKCCs contribute to the elevation of intracellular Cl − and resulting excitatory actions of GABA in ENS neurons.