Spatial and Temporal Dynamics in the Ionic Driving Force for GABA(A) Receptors

It is becoming increasingly apparent that the strength of GABAergic synaptic transmission is dynamic. One parameter that can establish differences in the actions of GABAergic synapses is the ionic driving force for the chloride-permeable GABA(A) receptor (GABA(A)R). Here we review some of the sophisticated ways in which this ionic driving force can vary within neuronal circuits. This driving force for GABA(A)Rs is subject to tight spatial control, with the distribution of Cl(−) transporter proteins and channels generating regional variation in the strength of GABA(A)R signalling across a single neuron. GABA(A)R dynamics can result from short-term changes in their driving force, which involve the temporary accumulation or depletion of intracellular Cl(−). In addition, activity-dependent changes in the expression and function of Cl(−) regulating proteins can result in long-term shifts in the driving force for GABA(A)Rs. The multifaceted regulation of the ionic driving force for GABA(A)Rs has wide ranging implications for mature brain function, neural circuit development, and disease.