title: SLC26A11 (KBAT) in Purkinje Cells Is Critical for Inhibitory Transmission and Contributes to Locomotor Coordination.
abstract: Chloride homeostasis determines the impact of inhibitory synaptic transmission and thereby mediates the excitability of neurons. Even though cerebellar Purkinje cells (PCs) receive a pronounced inhibitory GABAergic input from stellate and basket cells, the role of chloride homeostasis in these neurons is largely unknown. Here we studied at both the cellular and systems physiological level the function of a recently discovered chloride channel, SLC26A11 or kidney brain anion transporter (KBAT), which is prominently expressed in PCs. Using perforated patch clamp recordings of PCs, we found that a lack of KBAT channel in PC-specific KBAT KO mice (L7-KBAT KOs) induces a negative shift in the reversal potential of chloride as reflected in the GABAA-receptor-evoked currents, indicating a decrease in intracellular chloride concentration. Surprisingly, both in vitro and in vivo PCs in L7-KBAT KOs showed a significantly increased action potential firing frequency of simple spikes, which correlated with impaired motor performance on the Erasmus Ladder. Our findings support an important role for SLC26A11 in moderating chloride homeostasis and neuronal activity in the cerebellum.
authors.affiliation: Department of Neuroscience, Erasmus MC , 3000 CA Rotterdam, The Netherlands.
authors.forename: Negah
authors.identifier: 0000-0002-0709-5976
authors.initials: N
authors.lastname: Rahmati
authors.affiliation: Department of Neuroscience, Erasmus MC , 3000 CA Rotterdam, The Netherlands.
authors.forename: Maria Fernanda
authors.identifier: 0000-0002-2493-0769
authors.initials: MF
authors.lastname: Vinueza Veloz
authors.affiliation: Department of Medicine, University of Cincinnati , Cincinnati, OH 45267.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Medicine, University of Cincinnati , Cincinnati, OH 45267.
authors.forename: Sharon
authors.identifier: 0000-0001-5710-292X
authors.initials: S
authors.lastname: Barone
authors.affiliation: Department of Neuroscience, Erasmus MC , 3000 CA Rotterdam, The Netherlands.
authors.forename: Nahuel
authors.identifier: 0000-0001-5423-9883
authors.initials: N
authors.lastname: Rodolfo Ben Hamida
authors.affiliation: Department of Neuroscience, Erasmus MC , 3000 CA Rotterdam, The Netherlands.
authors.forename: Martijn
authors.identifier: 0000-0002-2675-1393
authors.initials: M
authors.lastname: Schonewille
authors.affiliation: Department of Neuroscience, Erasmus MC , 3000 CA Rotterdam, The Netherlands.
authors.forename: Freek E
authors.initials: FE
authors.lastname: Hoebeek
authors.affiliation: Department of Medicine, University of Cincinnati , Cincinnati, OH 45267.
authors.forename: Manoocher
authors.identifier: 0000-0003-4909-4469
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Department of Neuroscience, Erasmus MC, 3000 CA Rotterdam, The Netherlands; Netherlands Institute for Neuroscience, 1105 BA, Amsterdam, The Netherlands.
authors.forename: Chris I
authors.identifier: 0000-0001-5628-8187
authors.initials: CI
authors.lastname: De Zeeuw
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D005133:Eye Movements / Q000502:physiology; D005260:Female; D006706:Homeostasis / Q000502:physiology; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D011689:Purkinje Cells / Q000378:metabolism* / Q000473:pathology; D012027:Reflex, Vestibulo-Ocular / Q000502:physiology; D000076988:Sulfate Transporters; D009435:Synaptic Transmission / Q000502:physiology*; D046509:Tissue Culture Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000838:Anions; D018118:Chloride Channels; D002712:Chlorides; C000624312:Slc26a11 protein, mouse; D000076988:Sulfate Transporters; D005680:gamma-Aminobutyric Acid
keywords: Cerebellum; Chloride channel; Chloride homeostasis; GABAerg inhibition; Locomotion; Purkinje cell