Chloride Homeostasis in Neurons With Special Emphasis on the Olivocerebellar System: Differential Roles for Transporters and Channels

The intraneuronal ionic composition is an important determinant of brain functioning. There is growing evidence that aberrant homeostasis of the intracellular concentration of Cl- ([Cl-]i) evokes, in addition to that of Na+ and Ca2+, robust impairments of neuronal excitability and neurotransmission and thereby neurological conditions. More specifically, understanding the mechanisms underlying regulation of [Cl-]i is crucial for deciphering the variability in GABAergic and glycinergic signaling of neurons, in both health and disease. The homeostatic level of [Cl-]i is determined by various regulatory mechanisms, including those mediated by plasma membrane Cl- channels and transporters. This review focuses on the latest advances in identification, regulation and characterization of Cl- channels and transporters that modulate neuronal excitability and cell volume. By putting special emphasis on neurons of the olivocerebellar system, we establish that Cl- channels and transporters play an indispensable role in determining their [Cl-]i and thereby their function in sensorimotor coordination.