Abstract

Ligand-gated ion channels are of particular interest to the pharmaceutical industry for the treatment of diseases from a variety of therapeutic areas including CNS disorders, respiratory disease and chronic pain. Ligand-gated ion channels have historically been investigated using fluorescence-based and low throughput patch-clamp techniques. However the development of the Sophion Qube 384 automated patch-clamp system has allowed rapid exchange of liquid and direct measurement of ion channel currents on a millisecond timescale, making it possible to run HTS campaigns and support SAR with a functional readout. 

Here, we have used the Qube platform to assess the pharmacology of compounds with different modes of action on four members of the NMDA receptor family NR1/NR2A, NR2B, NR2C and NR2D. Additionally, we have developed a method for assessing voltage-dependent block of magnesium using a combined ligand- and voltage-gated protocol.