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.

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Keywords Cerebellar motor learning, Chloride homeostasis, Chloride transporters and channels, GABAergic inhibition, Olivocerebellar system
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Journal Frontiers in cellular neuroscience
Rahmati, N, Hoebeek, F.E, Peter, S, & de Zeeuw, C.I. (2018). Chloride homeostasis in neurons with special emphasis on the olivocerebellar system: Differential roles for transporters and channels. Frontiers in cellular neuroscience (Vol. 12). doi:10.3389/fncel.2018.00101