Key result
Deletion of SLC26A11 (KBAT) in Purkinje cells induced a negative shift in the reversal potential of GABA (-83.70 mV vs -72.88 mV) and increased action potential firing, impairing motor performance.
Absolute Event Rate: -83.7% vs -72.88%
p-value: p=0.03
SLC26A11 (KBAT) plays an important role in moderating chloride homeostasis and neuronal activity in cerebellar Purkinje cells, which is critical for locomotor coordination.
SLC26A11 deletion alters Purkinje cell excitability and motor coordination in mice; hypothesis-generating for cerebellar disorders but leaves open human relevance.
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.
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Rahmati et al. (2016) studied Normal physiology / Locomotor coordination. Deletion of SLC26A11 (KBAT) in Purkinje cells vs. Wild-type littermate controls was evaluated on Reversal potential of GABA (EGABA) (p=0.03). Deletion of SLC26A11 (KBAT) in Purkinje cells induced a negative shift in the reversal potential of GABA (-83.70 mV vs -72.88 mV) and increased action potential firing, impairing motor performance.
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