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. [ABSTRACT FROM AUTHOR]