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

TY - JOUR

T1 - Chloride Homeostasis in Neurons With Special Emphasis on the Olivocerebellar System: Differential Roles for Transporters and Channels

AU - Rahmati, Negah

AU - Hoebeek, Freek E

AU - Peter, Sasa

AU - De Zeeuw, Chris I.

PY - 2018/4

Y1 - 2018/4

N2 - 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 anddisease. 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.

AB - 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 anddisease. 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.

KW - chloride homeostasis

KW - chloride transporters and channels

KW - GABAergic inhibition

KW - olivocerebellar system

KW - cerebellar motor learning

U2 - 10.3389/fncel.2018.00101

DO - 10.3389/fncel.2018.00101

M3 - Article

SN - 1662-5102

VL - 12

JO - Frontiers in Cellular Neuroscience

JF - Frontiers in Cellular Neuroscience

M1 - 101

ER -