KCC2-Mediated Cl - Extrusion Modulates Spontaneous Hippocampal Network Events in Perinatal Rats and Mice

Inkeri Spoljaric, Albert Spoljaric, Martina Mavrovic, Patricia Seja, Martin Puskarjov, Kai Kaila

Cell Rep. 2019 Jan 29;26(5):1073-1081.e3.

PMID: 30699338

Abstract:

It is generally thought that hippocampal neurons of perinatal rats and mice lack transport-functional K-Cl cotransporter KCC2, and that Cl- regulation is dominated by Cl- uptake via the Na-K-2Cl cotransporter NKCC1. Here, we demonstrate a robust enhancement of spontaneous hippocampal network events (giant depolarizing potentials [GDPs]) by the KCC2 inhibitor VU0463271 in neonatal rats and late-gestation, wild-type mouse embryos, but not in their KCC2-null littermates. VU0463271 increased the depolarizing GABAergic synaptic drive onto neonatal CA3 pyramidal neurons, increasing their spiking probability and synchrony during the rising phase of a GDP. Our data indicate that Cl- extrusion by KCC2 is involved in modulation of GDPs already at their developmental onset during the perinatal period in mice and rats.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1391737011	VU0463271		1391737-01-1	Price