SLC26A11 (KBAT) in Purkinje Cells Is Critical for Inhibitory Transmission and Contributes to Locomotor Coordination

Autor: Chris I. De Zeeuw, Manoocher Soleimani, Martijn Schonewille, María Fernanda Vinueza Veloz, Sharon Barone, Jie Xu, Freek E. Hoebeek, Negah Rahmati, Nahuel Rodolfo Ben Hamida
Přispěvatelé: Netherlands Institute for Neuroscience (NIN)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: eNeuro, 3(3):e0028-16.2016. Society for Neuroscience
ISSN: 2373-2822
DOI: 10.1523/eneuro.0028-16.2016
Popis: 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, bothin vitroandin vivoPCs 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.
Databáze: OpenAIRE