Refer analysis of α1β2γ2 GABA type a receptor suggests a slight phase shift between principal and complementary subunits at the extracellular domain upon channel activation

Abstract

GABAa receptors are pentameric ligand gated ion channels and play a key role in synaptic inhibiton. Recently, structures of this receptor were revealed in closed and desensitized but not in the open state. However, the molecular mechanisms of the activation process remain elusive. We have made an attempt to address this issue by applying the REFER (φ-value) analysis which provides information on sequential movements of channel’s structural elements upon opening. Single-channel recordings from WT and selected single point mutants of the extracellular domain and interface of the α1β2γ2 receptor were performed and modeling was used to optimize the rate constants to determine the φ values.