Cerebellar purkinje cell: interacting Kv3 and Na currents influence firing (Akemann, Knopfel 2006)

 Download zip file   Auto-launch 
Help downloading and running models
Accession:80769
Purkinje neurons spontaneously generate action potentials in the absence of synaptic drive and thereby exert a tonic, yet plastic, input to their target cells in the deep cerebellar nuclei. Purkinje neurons express two ionic currents with biophysical properties that are specialized for high-frequency firing: resurgent sodium currents and potassium currents mediated by Kv3.3. Numerical simulations indicated that Kv3.3 increases the spontaneous firing rate via cooperation with resurgent sodium currents. We conclude that the rate of spontaneous action potential firing of Purkinje neurons is controlled by the interaction of Kv3.3 potassium currents and resurgent sodium currents. See paper for more and details.
Reference:
1 . Akemann W, Knopfel T (2006) Interaction of Kv3 potassium channels and resurgent sodium current influences the rate of spontaneous firing of Purkinje neurons. J Neurosci 26:4602-12 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s): Cerebellum purkinje cell;
Channel(s): I Na,t; I A; I K; I h; I K,Ca; I Calcium;
Gap Junctions:
Receptor(s):
Gene(s): Kv1.1 KCNA1; Kv4.3 KCND3; Kv3.3 KCNC3; HCN1;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Ion Channel Kinetics; Oscillations; Action Potentials; Calcium dynamics;
Implementer(s): Akemann, Walther [akemann at brain.riken.jp];
Search NeuronDB for information about:  Cerebellum purkinje cell; I Na,t; I A; I K; I h; I K,Ca; I Calcium;
This is the readme.txt for the model associated with the paper:

Akemann W, Knopfel T. Interaction of Kv3 potassium channels and
resurgent sodium current influences the rate of spontaneous firing of
Purkinje neurons. J Neurosci. 2006 Apr 26;26(17):4602-12.

These files were supplied by Akemann and Knopfel.

To use: simply autolaunch from ModelDB or 

1) download and extract the archive (zip file). 
2) Compile the mod files with the appropriate method (unix - run
nrnivmodl in the directory, mswin - run mknrndll in the directory
expanded from the archive, mac - drag the folder expanded from the
archive to the mknrndll icon in the Neuron folder)
3) run the model (in unix - nrngui mosinit.hoc, mswin - double click
on the mosinit.hoc file, mac - drag the mosinit.hoc file to the nrngui
icon in the Neuron folder)

6/8/2007 version updated: a short demonstration run has been added.

Akemann W, Knopfel T (2006) Interaction of Kv3 potassium channels and resurgent sodium current influences the rate of spontaneous firing of Purkinje neurons. J Neurosci 26:4602-12[PubMed]

References and models cited by this paper

References and models that cite this paper

Armstrong DM, Rawson JA (1979) Activity patterns of cerebellar cortical neurones and climbing fibre afferents in the awake cat. J Physiol 289:425-48 [PubMed]

Atzori M, Lau D, Tansey EP, Chow A, Ozaita A, Rudy B, McBain CJ (2000) H2 histamine receptor-phosphorylation of Kv3.2 modulates interneuron fast spiking. Nat Neurosci 3:791-8 [PubMed]

Bal T, McCormick DA (1997) Synchronized oscillations in the inferior olive are controlled by the hyperpolarization-activated cation current I(h). J Neurophysiol 77:3145-56 [Journal] [PubMed]

Behnisch T, Matsushita S, Knopfel T (2004) Imaging of gene expression during long-term potentiation. Neuroreport 15:2039-43

Benardo LS, Foster RE (1986) Oscillatory behavior in inferior olive neurons: mechanism, modulation, cell aggregates. Brain Res Bull 17:773-84 [PubMed]

Cerminara NL, Rawson JA (2004) Evidence that climbing fibers control an intrinsic spike generator in cerebellar Purkinje cells. J Neurosci 24:4510-7 [PubMed]

Chan E (1997) Regulation and function of Kv3.3 PhD thesis

Chung YH, Joo KM, Kim MJ, Cha CI (2003) Age-related changes in the distribution of Na(v)1.1 and Na(v)1.2 in rat cerebellum. Neuroreport 14:841-5

Do MT, Bean BP (2003) Subthreshold sodium currents and pacemaking of subthalamic neurons: modulation by slow inactivation. Neuron 39:109-20 [PubMed]

Do MT, Bean BP (2004) Sodium currents in subthalamic nucleus neurons from Nav1.6-null mice. J Neurophysiol 92:726-33 [Journal] [PubMed]

Edgerton JR, Reinhart PH (2003) Distinct contributions of small and large conductance Ca2+-activated K+ channels to rat Purkinje neuron function. J Physiol 548:53-69 [PubMed]

Erisir A, Lau D, Rudy B, Leonard CS (1999) Function of specific K(+) channels in sustained high-frequency firing of fast-spiking neocortical interneurons. J Neurophysiol 82:2476-89 [Journal] [PubMed]

Goldman-Wohl DS, Chan E, Baird D, Heintz N (1994) Kv3.3b: a novel Shaw type potassium channel expressed in terminally differentiated cerebellar Purkinje cells and deep cerebellar nuclei. J Neurosci 14:511-22 [PubMed]

GRANIT R, PHILLIPS CG (1956) Excitatory and inhibitory processes acting upon individual Purkinje cells of the cerebellum in cats. J Physiol 133:520-47 [PubMed]

Grieco TM, Malhotra JD, Chen C, Isom LL, Raman IM (2005) Open-channel block by the cytoplasmic tail of sodium channel beta4 as a mechanism for resurgent sodium current. Neuron 45:233-44 [PubMed]

Grieco TM, Raman IM (2004) Production of resurgent current in NaV1.6-null Purkinje neurons by slowing sodium channel inactivation with beta-pompilidotoxin. J Neurosci 24:35-42 [PubMed]

Hausser M, Clark BA (1997) Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration. Neuron 19:665-78 [PubMed]

Hausser M, Raman IM, Otis T, Smith SL, Nelson A, du Lac S, Loewenstein Y, Mahon S, Pennartz C (2004) The beat goes on: spontaneous firing in mammalian neuronal microcircuits. J Neurosci 24:9215-9 [PubMed]

Hines ML, Carnevale NT (1997) The NEURON simulation environment. Neural Comput 9:1179-209 [PubMed]

Itri JN, Michel S, Vansteensel MJ, Meijer JH, Colwell CS (2005) Fast delayed rectifier potassium current is required for circadian neural activity. Nat Neurosci 8:650-6 [PubMed]

Joho RH, Street C, Matsushita S, Knofipfel T (2006) Behavioral motor dysfunctionin Kv3-type potassium channel-deficient mice Genes Brain Behav (in press)

Kay AR, Sugimori M, Llinas R (1998) Kinetic and stochastic properties of a persistent sodium current in mature guinea pig cerebellar Purkinje cells. J Neurophysiol 80:1167-79 [Journal] [PubMed]

Khaliq ZM, Gouwens NW, Raman IM (2003) The contribution of resurgent sodium current to high-frequency firing in Purkinje neurons: an experimental and modeling study. J Neurosci 23:4899-912 [PubMed]

   Cerebellar Purkinje Cell: resurgent Na current and high frequency firing (Khaliq et al 2003) [Model]

Kohrman DC, Smith MR, Goldin AL, Harris J, Meisler MH (1996) A missense mutation in the sodium channel Scn8a is responsible for cerebellar ataxia in the mouse mutant jolting. J Neurosci 16:5993-9

Kullmann PH, Wheeler DW, Beacom J, Horn JP (2004) Implementation of a fast 16-Bit dynamic clamp using LabVIEW-RT. J Neurophysiol 91:542-54 [Journal] [PubMed]

   Sympathetic neuron (Wheeler et al 2004) [Model]

Lien CC, Jonas P (2003) Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons. J Neurosci 23:2058-68 [PubMed]

Llinas R, Sugimori M (1980) Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices. J Physiol 305:171-95 [PubMed]

Llinas R, Yarom Y (1986) Oscillatory properties of guinea-pig inferior olivary neurones and their pharmacological modulation: an in vitro study. J Physiol 376:163-82 [PubMed]

Martina M, Yao GL, Bean BP (2003) Properties and functional role of voltage-dependent potassium channels in dendrites of rat cerebellar Purkinje neurons. J Neurosci 23:5698-707 [PubMed]

Matsukawa H, Wolf AM, Matsushita S, Joho RH, Knopfel T (2003) Motor dysfunction and altered synaptic transmission at the parallel fiber-Purkinje cell synapse in mice lacking potassium channels Kv3.1 and Kv3.3. J Neurosci 23:7677-84

McKay BE, Molineux ML, Mehaffey WH, Turner RW (2005) Kv1 K+ channels control Purkinje cell output to facilitate postsynaptic rebound discharge in deep cerebellar neurons. J Neurosci 25:1481-92 [PubMed]

McKay BE, Turner RW (2004) Kv3 K+ channels enable burst output in rat cerebellar Purkinje cells. Eur J Neurosci 20:729-39 [PubMed]

McMahon A, Fowler SC, Perney TM, Akemann W, Knopfel T, Joho RH (2004) Allele-dependent changes of olivocerebellar circuit properties in the absence of the voltage-gated potassium channels Kv3.1 and Kv3.3. Eur J Neurosci 19:3317-27

Nelson AB, Krispel CM, Sekirnjak C, du Lac S (2003) Long-lasting increases in intrinsic excitability triggered by inhibition. Neuron 40:609-20 [PubMed]

Raman IM, Bean BP (1997) Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons. J Neurosci 17:4517-26 [PubMed]

Raman IM, Bean BP (1999) Ionic currents underlying spontaneous action potentials in isolated cerebellar Purkinje neurons. J Neurosci 19:1663-74 [PubMed]

Raman IM, Bean BP (2001) Inactivation and recovery of sodium currents in cerebellar Purkinje neurons: evidence for two mechanisms. Biophys J 80:729-37 [PubMed]

   Cerebellar Purkinje Cell: resurgent Na current and high frequency firing (Khaliq et al 2003) [Model]

Raman IM, Sprunger LK, Meisler MH, Bean BP (1997) Altered subthreshold sodium currents and disrupted firing patterns in Purkinje neurons of Scn8a mutant mice. Neuron 19:881-91 [PubMed]

Rudy B, Chow A, Lau D, Amarillo Y, Ozaita A, Saganich M, Moreno H, Nadal MS, Hernandez-Pineda (1999) Contributions of Kv3 channels to neuronal excitability. Ann N Y Acad Sci 868:304-43 [PubMed]

Rudy B, McBain CJ (2001) Kv3 channels: voltage-gated K+ channels designed for high-frequency repetitive firing. Trends Neurosci 24:517-26 [PubMed]

Sacco T, Tempia F (2002) A-type potassium currents active at subthreshold potentials in mouse cerebellar Purkinje cells. J Physiol 543:505-20

Sausbier M, Hu H, Arntz C, Feil S, Kamm S, Adelsberger H, Sausbier U, Sailer CA, Feil R, Hofm (2004) Cerebellar ataxia and Purkinje cell dysfunction caused by Ca2+-activated K+ channel deficiency. Proc Natl Acad Sci U S A 101:9474-8

Schaller KL, Caldwell JH (2003) Expression and distribution of voltage-gated sodium channels in the cerebellum. Cerebellum 2:2-9 [PubMed]

Shah BS, Stevens EB, Pinnock RD, Dixon AK, Lee K (2001) Developmental expression of the novel voltage-gated sodium channel auxiliary subunit beta3, in rat CNS. J Physiol 534:763-76

Smith SL, Otis TS (2003) Persistent changes in spontaneous firing of Purkinje neurons triggered by the nitric oxide signaling cascade. J Neurosci 23:367-72 [PubMed]

Song P, Yang Y, Barnes-Davies M, Bhattacharjee A, Hamann M, Forsythe ID, Oliver DL, Kaczmarek (2005) Acoustic environment determines phosphorylation state of the Kv3.1 potassium channel in auditory neurons. Nat Neurosci 8:1335-42 [PubMed]

Takahashi E, Nagasu T (2005) Pattern of compensatory expression of voltage-dependent Ca2+ channel alpha1 and beta subunits in brain of N-type Ca2+ channel alpha1B subunit gene-deficient mice with a CBA/JN genetic background. Exp Anim 54:29-36

Vega-Saenz de Miera EC, Rudy B, Sugimori M, Llinas R (1997) Molecular characterization of the sodium channel subunits expressed in mammalian cerebellar Purkinje cells. Proc Natl Acad Sci U S A 94:7059-64 [PubMed]

von Hehn CA, Bhattacharjee A, Kaczmarek LK (2004) Loss of Kv3.1 tonotopicity and alterations in cAMP response element-binding protein signaling in central auditory neurons of hearing impaired mice. J Neurosci 24:1936-40 [PubMed]

Weiser M, Vega-Saenz de Miera E, Kentros C, Moreno H, Franzen L, Hillman D, Baker H, Rudy B (1994) Differential expression of Shaw-related K+ channels in the rat central nervous system. J Neurosci 14:949-72 [PubMed]

Williams SR, Christensen SR, Stuart GJ, Hausser M (2002) Membrane potential bistability is controlled by the hyperpolarization-activated current I(H) in rat cerebellar Purkinje neurons in vitro. J Physiol 539:469-83 [PubMed]

Womack MD, Khodakhah K (2002) Characterization of large conductance Ca2+-activated K+ channels in cerebellar Purkinje neurons. Eur J Neurosci 16:1214-22 [PubMed]

Xu M, Welling A, Paparisto S, Hofmann F, Klugbauer N (2003) Enhanced expression of L-type Cav1.3 calcium channels in murine embryonic hearts from Cav1.2-deficient mice. J Biol Chem 278:40837-41 [PubMed]

Zerr P, Adelman JP, Maylie J (1998) Episodic ataxia mutations in Kv1.1 alter potassium channel function by dominant negative effects or haploinsufficiency. J Neurosci 18:2842-8

Akemann W, Lundby A, Mutoh H, Knopfel T (2009) Effect of voltage sensitive fluorescent proteins on neuronal excitability. Biophys J 96:3959-76 [Journal] [PubMed]

   Effect of voltage sensitive fluorescent proteins on neuronal excitability (Akemann et al. 2009) [Model]

Almog M, Korngreen A (2014) A Quantitative Description of Dendritic Conductances and Its Application to Dendritic Excitation in Layer 5 Pyramidal Neurons J Neurosci 34(1):182-196 [Journal]

   Ionic mechanisms of dendritic spikes (Almog and Korngreen 2014) [Model]

Anwar H, Hong S, De Schutter E (2012) Controlling Ca(2+)-Activated K (+) Channels with Models of Ca (2+) Buffering in Purkinje Cells. Cerebellum 11:681-693 [Journal] [PubMed]

   Controlling KCa channels with different Ca2+ buffering models in Purkinje cell (Anwar et al. 2012) [Model]

Carnevale NT, Morse TM (1996-2009) Research reports that have used NEURON Web published citations at the NEURON website [Journal]

Couto J, Linaro D, De Schutter E, Giugliano M (2015) On the Firing Rate Dependency Of the Phase Response Curves of rat Purkinje Neurons In Vitro PLOS Comp Biol [Journal] [PubMed]

   Phase response curves firing rate dependency of rat purkinje neurons in vitro (Couto et al 2015) [Model]

Desai R, Kronengold J, Mei J, Forman SA, Kaczmarek LK (2008) Protein kinase C modulates inactivation of Kv3.3 channels. J Biol Chem 283:22283-94 [PubMed]

Forrest MD (2015) Simulation of alcohol action upon a detailed Purkinje neuron model and a simpler surrogate model that runs >400 times faster BMC Neuroscience 16:27 [Journal] [PubMed]

   Alcohol action in a detailed Purkinje neuron model and an efficient simplified model (Forrest 2015) [Model]

Frey U, Egert U, Heer F, Hafizovic S, Hierlemann A (2009) Microelectronic system for high-resolution mapping of extracellular electric fields applied to brain slices. Biosens Bioelectron 24:2191-8 [Journal] [PubMed]

Huang S, Hong S, De Schutter E (2015) Non-linear leak currents affect mammalian neuron physiology. Front Cell Neurosci 9:432 [Journal] [PubMed]

   Concentration dependent nonlinear K+ and Cl- leak current (Huang et al. 2015) [Model]

Kole MH, Ilschner SU, Kampa BM, Williams SR, Ruben PC, Stuart GJ (2008) Action potential generation requires a high sodium channel density in the axon initial segment. Nat Neurosci 11:178-86 [Journal] [PubMed]

   [1 reconstructed morphology on NeuroMorpho.Org]
   Na+ channel dependence of AP initiation in cortical pyramidal neuron (Kole et al. 2008) [Model]

Masoli S, Solinas S, D'Angelo E (2015) Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization. Front Cell Neurosci 9:47 [Journal] [PubMed]

   A detailed Purkinje cell model (Masoli et al 2015) [Model]

Mercer JN, Chan CS, Tkatch T, Held J, Surmeier DJ (2007) Nav1.6 sodium channels are critical to pacemaking and fast spiking in globus pallidus neurons. J Neurosci 27:13552-66 [Journal] [PubMed]

   Nav1.6 sodium channel model in globus pallidus neurons (Mercer et al. 2007) [Model]

Traub RD, Middleton SJ, Knopfel T, Whittington MA (2008) Model of very fast (greater than 75 Hz) network oscillations generated by electrical coupling between the proximal axons of cerebellar Purkinje cells. Eur J Neurosci 28:1603-16 [Journal]

   Axonal gap junctions produce fast oscillations in cerebellar Purkinje cells (Traub et al. 2008) [Model]

(67 refs)