efficacy of synaptic inhibition depends on multiple, dynamically interacting mechanisms implicated in chloride homeostasis突触抑制的效果取决于多个动态相互作用机制涉及氯体内平衡.pdfVIP

Efficacy of Synaptic Inhibition Depends on Multiple, Dynamically Interacting Mechanisms Implicated in Chloride Homeostasis 1,2 3 1,2 1 ¨ 4 Nicolas Doyon , Steven A. Prescott , Annie Castonguay , Antoine G. Godin , Helmut Kroger , Yves De Koninck1,2* ´ ´ ´ 1 Division of Cellular and Molecular Neuroscience, Centre de recherche Universite Laval Robert-Giffard, Quebec, Quebec, Canada, 2 Department of Psychiatry ´ ´ ´ Neuroscience, Universite Laval, Quebec, Quebec, Canada, 3 Department of Neurobiology and Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, ´ ´ ´ Pennsylvania, United States of America, 4 Department of Physics, Universite Laval, Quebec, Quebec, Canada Abstract Chloride homeostasis is a critical determinant of the strength and robustness of inhibition mediated by GABAA receptors (GABAARs). The impact of changes in steady state Cl2 gradient is relatively straightforward to understand, but how dynamic interplay between Cl2 influx, diffusion, extrusion and interaction with other ion species affects synaptic signaling remains uncertain. Here we used electrodiffusion modeling to investigate the nonlinear interactions between these processes. Results demonstrate that diffusion is crucial for redistributing intracellular Cl2 load on a fast time scale, whereas Cl2extrusion controls steady state levels. Interaction between diffusion and extrusion