Inhibition Gets a New KAR Smell.

Inhibition Gets a New KAR Smell. Epilepsy Curr. 2019 Apr 29;:1535759719843277 Authors: Courtney CD, Christian CA Abstract Ionotropic and metabotropic kainate receptor signaling regulates Cl- homeostasis and GABAergic inhibition Garand D, Mahadevan V, Woodin MA. J Physiol. 2018. doi:10.1113/JP276901 Potassium chloride cotransporter 2 (KCC2) plays a critical role in the regulation of chloride (Cl-) homeostasis within mature neurons. The KCC2 is a secondarily active transporter that extrudes Cl- from the neuron, which maintains a low intracellular Cl-concentration [Cl-]. This results in a hyperpolarized reversal potential of GABA ( E GABA), which is required for fast synaptic inhibition in the mature central nervous system. Potassium chloride cotransporter 2 also plays a structural role in dendritic spines and at excitatory synapses and interacts with "excitatory" proteins, including the GluK2 subunit of kainate receptors (KARs). Kainate receptors are glutamate receptors that display both ionotropic and metabotropic signaling. We show that activating KARs in the hippocampus hyperpolarizes E GABA, thus strengthening inhibition. This hyperpolarization occurs via both ionotropic and metabotropic KAR signaling in the CA3 region, whereas it is absent in the GluK1/2-/- mouse, and is independent of zinc release from mossy fiber terminals. The metabotropic signaling mechanism is dependent on KCC2, although the ionotropic signaling mechanism pro...
Source: Epilepsy Currents - Category: Neurology Tags: Epilepsy Curr Source Type: research