title: KV 10.1 opposes activity-dependent increase in Ca²⁺ influx into the presynaptic terminal of the parallel fibre-Purkinje cell synapse.
abstract: Voltage-gated KV 10.1 potassium channels are widely expressed in the mammalian brain but their function remains poorly understood. We report that KV 10.1 is enriched in the presynaptic terminals and does not take part in somatic action potentials. In parallel fibre synapses in the cerebellar cortex, we find that KV 10.1 regulates Ca(2+) influx and neurotransmitter release during repetitive high-frequency activity. Our results describe the physiological role of mammalian KV 10.1 for the first time and help understand the fine-tuning of synaptic transmission. The voltage-gated potassium channel KV 10.1 (Eag1) is widely expressed in the mammalian brain, but its physiological function is not yet understood. Previous studies revealed highest expression levels in hippocampus and cerebellum and suggested a synaptic localization of the channel. The distinct activation kinetics of KV 10.1 indicate a role during repetitive activity of the cell. Here, we confirm the synaptic localization of KV 10.1 both biochemically and functionally and that the channel is sufficiently fast at physiological temperature to take part in repolarization of the action potential (AP). We studied the role of the channel in cerebellar physiology using patch clamp and two-photon Ca(2+) imaging in KV 10.1-deficient and wild-type mice. The excitability and action potential waveform recorded at granule cell somata was unchanged, while Ca(2+) influx into axonal boutons was enhanced in mutants in response to stimulation with three APs, but not after a single AP. Furthermore, mutants exhibited a frequency-dependent increase in facilitation at the parallel fibre-Purkinje cell synapse at high firing rates. We propose that KV 10.1 acts as a modulator of local AP shape specifically during high-frequency burst firing when other potassium channels suffer cumulative inactivation.
authors.affiliation: Max-Planck-Institute of Experimental Medicine, 37075, Göttingen, Germany; International Max Planck Research School Neurosciences, 37077, Göttingen, Germany.
authors.forename: Lena Sünke
authors.initials: LS
authors.lastname: Mortensen
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schmidt
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Farsi
authors.forename: Alonso
authors.initials: A
authors.lastname: Barrantes-Freer
authors.forename: María E
authors.initials: ME
authors.lastname: Rubio
authors.forename: Roser
authors.initials: R
authors.lastname: Ufartes
authors.forename: Jens
authors.initials: J
authors.lastname: Eilers
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakaba
authors.forename: Walter
authors.initials: W
authors.lastname: Stühmer
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pardo
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D051638:Ether-A-Go-Go Potassium Channels / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D057809:HEK293 Cells; D006801:Humans; D018345:Mice, Knockout; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; C489605:Kcng3 protein, mouse; D024642:Potassium Channels, Voltage-Gated; D002118:Calcium