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K V 10.1 opposes activity‐dependent increase in Ca 2+ influx into the presynaptic terminal of the parallel fibre–Purkinje cell synapse
Author(s) -
Mortensen Lena Sünke,
Schmidt Hartmut,
Farsi Zohreh,
BarrantesFreer Alonso,
Rubio María E.,
Ufartes Roser,
Eilers Jens,
Sakaba Takeshi,
Stühmer Walter,
Pardo Luis A.
Publication year - 2014
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2014.281600
Subject(s) - neurotransmission , neuroscience , synapse , purkinje cell , cerebellum , biophysics , chemistry , potassium channel , neurotransmitter , patch clamp , cerebellar cortex , stimulation , microbiology and biotechnology , biology , electrophysiology , biochemistry , central nervous system , receptor
Key points Voltage‐gated K V 10.1 potassium channels are widely expressed in the mammalian brain but their function remains poorly understood. We report that K V 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 K V 10.1 regulates Ca 2+ influx and neurotransmitter release during repetitive high‐frequency activity. Our results describe the physiological role of mammalian K V 10.1 for the first time and help understand the fine‐tuning of synaptic transmission.Abstract The voltage‐gated potassium channel K V 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 K V 10.1 indicate a role during repetitive activity of the cell. Here, we confirm the synaptic localization of K V 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 K V 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 K V 10.1 acts as a modulator of local AP shape specifically during high‐frequency burst firing when other potassium channels suffer cumulative inactivation.