Functional Modifications of Acid-Sensing Ion Channels by Ligand-Gated Chloride Channels
Copyright policy )Functional Modifications of Acid-Sensing Ion Channels by Ligand-Gated Chloride Channels
Together, acid-sensing ion channels (ASICs) and epithelial sodium channels (ENaC) constitute the majority of voltage-independent sodium channels in mammals. ENaC is regulated by a chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Here we show that ASICs were reversibly inhibited by activation of GABA(A) receptors in murine hippocampal neurons. This inhibition of ASICs required opening of the chloride channels but occurred with both outward and inward GABA(A) receptor-mediated currents. Moreover, activation of the GABA(A) receptors modified the pharmacological features and kinetic properties of the ASIC currents, including the time course of activation, desensitization and deactivation. Modification of ASICs by open GABA(A) receptors was also observed in both nucleated patches and outside-out patches excised from hippocampal neurons. Interestingly, ASICs and GABA(A) receptors interacted to regulate synaptic plasticity in CA1 hippocampal slices. The activation of glycine receptors, which are similar to GABA(A) receptors, also modified ASICs in spinal neurons. We conclude that GABA(A) receptors and glycine receptors modify ASICs in neurons through mechanisms that require the opening of chloride channels.
- Robarts Research Institute, London, Canada Canada
- University of Toronto Canada
- Western University Canada
- Sunnybrook Health Science Centre Canada
- University of New Hampshire United States
Patch-Clamp Techniques, Science, Intracellular Space, Nerve Tissue Proteins, In Vitro Techniques, Hippocampus, Sodium Channels, Mice, Receptors, Glycine, Chlorides, Chloride Channels, Animals, gamma-Aminobutyric Acid, Ions, Neurons, Neuronal Plasticity, Q, R, Ligand-Gated Ion Channels, Receptors, GABA-A, Acid Sensing Ion Channels, Kinetics, Medicine, Ion Channel Gating, Research Article
Patch-Clamp Techniques, Science, Intracellular Space, Nerve Tissue Proteins, In Vitro Techniques, Hippocampus, Sodium Channels, Mice, Receptors, Glycine, Chlorides, Chloride Channels, Animals, gamma-Aminobutyric Acid, Ions, Neurons, Neuronal Plasticity, Q, R, Ligand-Gated Ion Channels, Receptors, GABA-A, Acid Sensing Ion Channels, Kinetics, Medicine, Ion Channel Gating, Research Article
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