Overview
- Kozek, K.A. et al. (2018) ACS Chem. Neurosci. doi: 10.1021/acschemneuro.8b00287.
VU0529331 is an activator of the homomeric and of non-GIRK1-containing GIRK channels. The activity of the compound is much stronger on non-GIRK1/X channels. VU0529331 does not change the potassium selectivity or rectification of GIRK channels1. VU0529331 activates GIRK2 and GIRK4 homomeric channels expressed in HEK293 cells and demonstrates EC50 values of 5.1 and 22.3 µM respectively1.
The GIRK family, also known as the Kir3 family, is part of the larger inwardly rectifying potassium channel (Kir) family. GIRK channels play an important role in the regulation of cellular excitability. GIRK channels are heterotetrameric or homotetrameric combinations of the GIRK1−GIRK4 subunits. GIRK channels are associated with a variety of neurological disorders and alcohol and drug addiction1,2.
Alomone Labs VU0529331 activates homomeric non-GIRK1-containing GIRK channels expressed in Xenopus oocytes. Representative currents of GIRK2 (Kir3.2) channels (left) and GIRK4 (Kir3.4) channels (right), measured in high K+-containing bath solution at a holding potential of -80 mV. Currents were dose-dependently activated by 25-seconds rapid perfusion with 1 µM, 5 µM, 20 µM and 60 µM VU0529331 (#V-155), as indicated (color legend bottom right). Bar charts in insets (bottom left) show the average effects of VU0529331 concentration on each channel type.
Data was kindly provided by Prof. Nathan Dascal, Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Israel.
