Kv1 potassium channels control action potential firing of putative GABAergic deep cerebellar nuclear neurons

Abstract

ABSTRACTThe Kv1 voltage-gated potassium channels (kv1.1-1.8) display characteristic low-threshold activation ranges what enables their role in regulating diverse aspects of neuronal function, such as the action potential (AP) threshold and waveform, and thereby influence neuronal excitability or synaptic transmission. Kv1 channels are highly expressed in the cerebellar cortex and nuclei and mutations of human Kv1 genes are associated to episodic forms of ataxia (EAT-1). Besides the well-established role of Kv1 channels in regulating the basket-Purkinje cells inhibitory synapses of cerebellar cortex, cerebellar Kv1 channels regulate the principal deep cerebellar nuclear neurons activity (DCNs). DCNs however, include as well different groups of GABAergic cells that project locally to target principal DCNs, or to the inferior-olive or recurrently to the cerebellar cortex, but whether their function is controlled by Kv1 channels remains unclear. Here, using cerebellar slices from the GAD67-GFP line mice to identify putative GABAergic-DCNs and specific Kv1 channel blockers (dendrotoxins-alpha/I/K (DTXs)) we provide evidence that putative GABAergic-DCNs spontaneous and evoked activity is controlled by Kv1 currents. DTXs shifted in the hyperpolarizing direction the voltage threshold of spontaneous APs in GABAergic-DCNs, increased GABAergic-DCNs spontaneous firing rate and decreased these neurons ability to fire repetitively action potentials at high frequency. Moreover, in spontaneously silent putative nucleo-cortical DCNs, DTXs application induced depolarization and tonic firing. These results strongly suggest that Kv1 channels regulate GABAergic-DCNs activity and thereby can control previously unrecognized aspects of cerebellar function.