Chloride cotransporter KCC2 is essential for GABAergic inhibition in the SCN.

This study investigates the role of KCC2 on GABA-induced Ca2+ transients in SCN neurons from mice exposed to different photoperiods. We show for the first time that blocking KCC2 with the newly developed blocker ML077 can cause a shift in the polarity of the GABAergic response. This will increase the amount of excitatory responses in SCN neurons and thus cause a shift in excitatory/inhibitory ratio. These results indicate that KCC2 is an essential component in regulating [Cl-]i and the equilibrium potential of Cl- and thereby determining the sign of the GABAergic response. Moreover, our data suggest a role for the Cl- cotransporters in the switch from inhibition to excitation observed under long day photoperiod. PMID: 29782876 [PubMed - as supplied by publisher]
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research