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

eNeuro. 2016 Jun 15;3(3):ENEURO.0028-16.2016. doi: 10.1523/ENEURO.0028-16.2016. eCollection May-Jun 2016.

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.

Keywords: Cerebellum; Chloride channel; Chloride homeostasis; GABAerg inhibition; Locomotion; Purkinje cell.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anions / metabolism
  • Chloride Channels / genetics
  • Chloride Channels / metabolism*
  • Chlorides / metabolism
  • Eye Movements / physiology
  • Female
  • Homeostasis / physiology
  • Interneurons / metabolism
  • Interneurons / pathology
  • Male
  • Membrane Potentials / physiology
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / physiology*
  • Neural Inhibition / physiology*
  • Purkinje Cells / metabolism*
  • Purkinje Cells / pathology
  • Reflex, Vestibulo-Ocular / physiology
  • Synaptic Transmission / physiology*
  • Tissue Culture Techniques
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Anions
  • Chloride Channels
  • Chlorides
  • Slc26a11 protein, mouse
  • gamma-Aminobutyric Acid