Abstract
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 Ca(2+), 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.