Figure 1: CCCs control GABAA receptor-mediated inhibition. Panels (a) and (b) show the effects of NKCC1 activity in the absence (panel (a)) or presence (panel (b)) of GABA. NKCC1 mediates the electroneutral cotransport of Na+, K+, and 2 Cl−, increasing the intracellular Cl- concentration. As a result, upon binding of GABA upon the GABAA receptor, the channel pore opens and Cl leaves the neuron, causing a depolarization. Panels c and d show the effects of NKCC1 activity on GABAA receptor function in the absence (panel c) or presence (panel d) of GABA. KCC2 in contrast exports K+ and Cl- reducing intracellular Cl-. Activation of receptors therefore results into influx of Cl and hyperpolarizing current. Their function is dependent upon the gradients of Na+ and K+, which are controlled by various factors, including background conductances, membrane voltage, and by the Na+/K+ ATPase.