Efficacy of Synaptic Inhibition Depends on Multiple, Dynamically Interacting Mechanisms Implicated in Chloride Homeostasis

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 Cl− gradient is relatively straightforward to understand, but how dynamic interplay between Cl− 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 Cl− load on a fast time scale, whereas Cl−extrusion controls steady state levels. Interaction between diffusion and extrusion can result in a somato-dendritic Cl− gradient even when KCC2 is distributed uniformly across the cell. Reducing KCC2 activity led to decreased efficacy of GABAAR-mediated inhibition, but increasing GABAAR input failed to fully compensate for this form of disinhibition because of activity-dependent accumulation of Cl−. Furthermore, if spiking persisted despite the presence of GABAAR input, Cl− accumulation became accelerated because of the large Cl− driving force that occurs during spikes. The resulting positive feedback loop caused catastrophic failure of inhibition. Simulations also revealed other feedback loops, such as competition between Cl− and pH regulation. Several model predictions were tested and confirmed by [Cl−]i imaging experiments. Our study has thus uncovered how Cl− regulation depends on a multiplicity of dynamically interacting mechanisms. Furthermore, the model revealed that enhancing KCC2 activity beyond normal levels did not negatively impact firing frequency or cause overt extracellular K− accumulation, demonstrating that enhancing KCC2 activity is a valid strategy for therapeutic intervention

Dinâmica da água no solo em talude de corte submetido a diferentes práticas vegetativas.

A presente pesquisa foi baseada em um experimento em andamento localizado no Aeroporto Internacional do Rio de Janeiro Galeão/ Antônio Carlos Jobim (Ilha do Governador, Rio de Janeiro, RJ). Seu objetivo é o de avaliar a dinâmica da água no solo e caracterizar os mecanismos hidrológicos envolvidos nos processos de implantação de vegetação em um talude de corte recentemente conformado. Para tanto foi implantada instrumentação para medição de potenciais matriciais, umidade volumétrica e precipitação logo após a implantação das práticas vegetativas. A metodologia utilizada, que consistiu de medições horárias de todos os parâmetros, mostrou ser uma excelente ferramenta na detecção dos mecanismos envolvidos na dinâmica da água no solo. A rápida resposta dos sistemas avaliados indica a importância de avaliações numa escala temporal detalhada, onde os eventos possam ser analisados individualmente