TY - JOUR T1 - Cerebellar stellate cell excitability is coordinated by shifts in the gating behavior of voltage-gated Na<sup>+</sup> and A-type K<sup>+</sup> channels JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0126-19.2019 SP - ENEURO.0126-19.2019 AU - Ryan P.D. Alexander AU - John Mitry AU - Vasu Sareen AU - Anmar Khadra AU - Derek Bowie Y1 - 2019/05/20 UR - http://www.eneuro.org/content/early/2019/05/20/ENEURO.0126-19.2019.abstract N2 - Neuronal excitability in the vertebrate brain is governed by the coordinated activity of both ligand- and voltage-gated ion channels. In the cerebellum, spontaneous action potential (AP) firing of inhibitory stellate cells (SCs) is variable, typically operating within the 5-30 Hz frequency range. AP frequency is shaped by the activity of somatodendritic A-type K+ channels and the inhibitory effect of GABAergic transmission. An added complication, however, is that whole-cell recording from SCs induces a time-dependent and sustained increase in membrane excitability making it difficult to define the full range of firing rates. Here, we show that whole-cell recording in cerebellar SCs of both male and female mice augments firing rates by reducing the membrane potential at which APs are initiated. AP threshold is lowered due to a hyperpolarizing shift in the gating behavior of voltage-gated Na+ channels. Whole-cell recording also elicits a hyperpolarizing shift in the gating behavior of A-type K+ channels which contributes to increased firing rates. Hodgkin-Huxley modeling and pharmacological experiments reveal that gating shifts in A-type K+ channel activity do not impact AP threshold, but rather promote channel inactivation which removes restraint on the upper limit of firing rates. Taken together, our work reveals an unappreciated impact of voltage-gated Na+ channels that work in coordination with A-type K+ channels to regulate the firing frequency of cerebellar SCs.Significance Statement The cerebellum is a brain region that fulfills critical roles in motor function in adults as well as being linked to neurodevelopmental disorders in the developing brain. Significant attention has been directed towards understanding connectivity within the cerebellum and how its neuronal circuits are regulated. Stellate cells are inhibitory GABAergic interneurons that make-up neuronal circuits that control the output from the cerebral cortex by regulating the firing properties of Purkinje cells. The strength of GABAergic inhibition of Purkinje cells is governed by the excitability of stellate cells which fire action potentials at a wide range of frequencies. Our study reveals an unappreciated role of voltage-gated sodium channels that work in coordination with A-type K+-channels to establish stellate cell firing rates. ER -