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.
Footnotes
↵1 The authors declare no competing financial interests.
↵3 This work was supported by the Dutch Organization for Medical Sciences (ZonMw Top-Go 912.100.00; C.I.D.Z.), Life Sciences (ALW 854.10.004; C.I.D.Z.), Senter (Neurobsik FES 0908 min VWS; C.I.D.Z.), the ERC-advanced and related ERC-POCs (294775), Cerebnet (238686 ITN), and C7 (238214 ITN) programs of the European Community (C.I.D.Z.); M. Soleimani was supported by Merit Review award 510BX001000-04 from the Department of Veterans Affairs, and funds from the Center on Genetics of Transport and Epithelial Biology at University of Cincinnati. We thank Mandy Rutteman and Elise Haasdijk for technical assistance.
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