Activation of the α1β2γ2L GABAA Receptor by Physiological Agonists

The Cl- permeable GABA(A) receptor is a major contributor to cellular inhibition in the brain. The receptor is normally activated by synaptically-released or ambient GABA but is sensitive to a number of physiological compounds such as beta-alanine, taurine, and neurosteroids that, to various degrees, activate the receptor and modulate responses either to the transmitter or to each other. Here, we describe alpha 1 beta 2 gamma 2L GABA(A) receptor activation and modulation by combinations of orthosteric and allosteric activators. The overall goal was to gain insight into how changes in the levels of endogenous agonists modulate receptor activity and influence cellular inhibition. Experimental observations and simulations are described in the framework of a cyclic concerted transition model. We also provide general analytical solutions for the analysis of electrophysiological data collected in the presence of combinations of active compounds.

Automated summary

The study focused on the activation and modulation of the Cl- permeable GABA(A) receptor, revealing its sensitivity to various physiological compounds and their interactions as activators. The findings contribute to understanding how changes in endogenous agonists levels modulate receptor activity and cellular inhibition.