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Erg potassium currents of neonatal mouse Purkinje cells exhibit fast gating kinetics and are inhibited by mGluR1 activation

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Erg potassium currents of neonatal mouse Purkinje cells exhibit fast gating kinetics and are inhibited by mGluR1 activation. / Niculescu, Dragos; Hirdes, Wiebke; Hornig, Sönke; Pongs, Olaf; Schwarz, Juergen.

in: J NEUROSCI, Jahrgang 33, Nr. 42, 16.10.2013, S. 16729-40.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Niculescu, D, Hirdes, W, Hornig, S, Pongs, O & Schwarz, J 2013, 'Erg potassium currents of neonatal mouse Purkinje cells exhibit fast gating kinetics and are inhibited by mGluR1 activation', J NEUROSCI, Jg. 33, Nr. 42, S. 16729-40. https://doi.org/10.1523/JNEUROSCI.5523-12.2013

APA

Niculescu, D., Hirdes, W., Hornig, S., Pongs, O., & Schwarz, J. (2013). Erg potassium currents of neonatal mouse Purkinje cells exhibit fast gating kinetics and are inhibited by mGluR1 activation. J NEUROSCI, 33(42), 16729-40. https://doi.org/10.1523/JNEUROSCI.5523-12.2013

Vancouver

Niculescu D, Hirdes W, Hornig S, Pongs O, Schwarz J. Erg potassium currents of neonatal mouse Purkinje cells exhibit fast gating kinetics and are inhibited by mGluR1 activation. J NEUROSCI. 2013 Okt 16;33(42):16729-40. https://doi.org/10.1523/JNEUROSCI.5523-12.2013

Bibtex

@article{0cb0bc02119a4aac9ce706cc341be07f,
title = "Erg potassium currents of neonatal mouse Purkinje cells exhibit fast gating kinetics and are inhibited by mGluR1 activation",
abstract = "We investigated the subthreshold properties of an erg (ether-{\`a}-go-go-related gene) K(+) current in Purkinje cells of neonatal mice. Action potentials recorded from Purkinje cells in cerebellar slices exhibited a decreased threshold potential and increased frequency of spontaneous and repetitive activity following application of the specific erg channel blocker E-4031. Accommodation was absent before and after drug application. The erg current of these Purkinje cells activated at membrane potentials near -60 mV and exhibited fast gating kinetics. The functional importance of fast gating subthreshold erg channels in Purkinje cells was corroborated by comparing the results of action potential clamp experiments with erg1a, erg1b, erg2, and erg3 currents heterologously expressed in HEK cells. Computer simulations based on a NEURON model of Purkinje cells only reproduced the effects of the native erg current when an erg channel conductance like that of erg3 was included. Experiments with subunit-sensitive toxins (BeKm-1, APETx1) indicated that erg channels in Purkinje cells are presumably mediated by heteromeric erg1/erg3 or modified erg1 channels. Following mGluR1 activation, the native erg current was reduced by ∼70%, brought about by reduction of the maximal erg current and a shift of the activation curve to more positive potentials. The Purkinje cell erg current contributed to the sustained current component of the biphasic mGluR1 response. Activation of mGluR1 by the agonist 3,4-dihydroxyphenylglycol increased Purkinje cell excitability, similar to that induced by E-4031. The results indicated that erg currents can be modulated and may contribute to the mGluR1-induced plasticity changes in Purkinje cells.",
keywords = "Action Potentials, Animals, Cerebellum, Cnidarian Venoms, Computer Simulation, Ether-A-Go-Go Potassium Channels, Excitatory Amino Acid Agonists, HEK293 Cells, Humans, Male, Membrane Potentials, Mice, Models, Neurological, Purkinje Cells, Receptors, Metabotropic Glutamate, Scorpion Venoms, Sesquiterpenes",
author = "Dragos Niculescu and Wiebke Hirdes and S{\"o}nke Hornig and Olaf Pongs and Juergen Schwarz",
year = "2013",
month = oct,
day = "16",
doi = "10.1523/JNEUROSCI.5523-12.2013",
language = "English",
volume = "33",
pages = "16729--40",
journal = "J NEUROSCI",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "42",

}

RIS

TY - JOUR

T1 - Erg potassium currents of neonatal mouse Purkinje cells exhibit fast gating kinetics and are inhibited by mGluR1 activation

AU - Niculescu, Dragos

AU - Hirdes, Wiebke

AU - Hornig, Sönke

AU - Pongs, Olaf

AU - Schwarz, Juergen

PY - 2013/10/16

Y1 - 2013/10/16

N2 - We investigated the subthreshold properties of an erg (ether-à-go-go-related gene) K(+) current in Purkinje cells of neonatal mice. Action potentials recorded from Purkinje cells in cerebellar slices exhibited a decreased threshold potential and increased frequency of spontaneous and repetitive activity following application of the specific erg channel blocker E-4031. Accommodation was absent before and after drug application. The erg current of these Purkinje cells activated at membrane potentials near -60 mV and exhibited fast gating kinetics. The functional importance of fast gating subthreshold erg channels in Purkinje cells was corroborated by comparing the results of action potential clamp experiments with erg1a, erg1b, erg2, and erg3 currents heterologously expressed in HEK cells. Computer simulations based on a NEURON model of Purkinje cells only reproduced the effects of the native erg current when an erg channel conductance like that of erg3 was included. Experiments with subunit-sensitive toxins (BeKm-1, APETx1) indicated that erg channels in Purkinje cells are presumably mediated by heteromeric erg1/erg3 or modified erg1 channels. Following mGluR1 activation, the native erg current was reduced by ∼70%, brought about by reduction of the maximal erg current and a shift of the activation curve to more positive potentials. The Purkinje cell erg current contributed to the sustained current component of the biphasic mGluR1 response. Activation of mGluR1 by the agonist 3,4-dihydroxyphenylglycol increased Purkinje cell excitability, similar to that induced by E-4031. The results indicated that erg currents can be modulated and may contribute to the mGluR1-induced plasticity changes in Purkinje cells.

AB - We investigated the subthreshold properties of an erg (ether-à-go-go-related gene) K(+) current in Purkinje cells of neonatal mice. Action potentials recorded from Purkinje cells in cerebellar slices exhibited a decreased threshold potential and increased frequency of spontaneous and repetitive activity following application of the specific erg channel blocker E-4031. Accommodation was absent before and after drug application. The erg current of these Purkinje cells activated at membrane potentials near -60 mV and exhibited fast gating kinetics. The functional importance of fast gating subthreshold erg channels in Purkinje cells was corroborated by comparing the results of action potential clamp experiments with erg1a, erg1b, erg2, and erg3 currents heterologously expressed in HEK cells. Computer simulations based on a NEURON model of Purkinje cells only reproduced the effects of the native erg current when an erg channel conductance like that of erg3 was included. Experiments with subunit-sensitive toxins (BeKm-1, APETx1) indicated that erg channels in Purkinje cells are presumably mediated by heteromeric erg1/erg3 or modified erg1 channels. Following mGluR1 activation, the native erg current was reduced by ∼70%, brought about by reduction of the maximal erg current and a shift of the activation curve to more positive potentials. The Purkinje cell erg current contributed to the sustained current component of the biphasic mGluR1 response. Activation of mGluR1 by the agonist 3,4-dihydroxyphenylglycol increased Purkinje cell excitability, similar to that induced by E-4031. The results indicated that erg currents can be modulated and may contribute to the mGluR1-induced plasticity changes in Purkinje cells.

KW - Action Potentials

KW - Animals

KW - Cerebellum

KW - Cnidarian Venoms

KW - Computer Simulation

KW - Ether-A-Go-Go Potassium Channels

KW - Excitatory Amino Acid Agonists

KW - HEK293 Cells

KW - Humans

KW - Male

KW - Membrane Potentials

KW - Mice

KW - Models, Neurological

KW - Purkinje Cells

KW - Receptors, Metabotropic Glutamate

KW - Scorpion Venoms

KW - Sesquiterpenes

U2 - 10.1523/JNEUROSCI.5523-12.2013

DO - 10.1523/JNEUROSCI.5523-12.2013

M3 - SCORING: Journal article

C2 - 24133274

VL - 33

SP - 16729

EP - 16740

JO - J NEUROSCI

JF - J NEUROSCI

SN - 0270-6474

IS - 42

ER -