Rescue of Motor Coordination by Purkinje Cell-Targeted Restoration of Kv3.3 Channels in<i>Kcnc3</i>-Null Mice Requires<i>Kcnc1</i>

Hurlock, Edward C.; Bose, Mitali; Pierce, Ganon; Joho, Rolf H.

doi:10.1523/jneurosci.4048-09.2009

Cited by 35 publications

(44 citation statements)

References 49 publications

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“…These differences were not immediately discernible in the Npc1 +/-mice by visual inspection, but were detected using a sensitive computer-assisted locomotor array in the open-field +/+ mice, demonstrating an increase in stride length and duration concomitant with decreased stride frequency. This is a surprising result, as animals with cerebellar ataxia usually present with decreased stride length and duration accompanied by an increase in stride frequency [31,34,35]. Given that Npc1 +/-mice presented with an intermediate voluntary movement phenotype, we expected these mice to also have moderate gait abnormalities.…”

Section: Discussionmentioning

confidence: 98%

Neurological Dysfunction in Early Maturity of a Model for Niemann–Pick C1 Carrier Status

et al. 2016

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Autosomal recessive inheritance of NPC1 with loss-of-function mutations underlies Niemann-Pick disease, type C1 (NP-C1), a lysosomal storage disorder with progressive neurodegeneration. It is uncertain from limited biochemical studies and patient case reports whether NPC1 haploinsufficiency can cause a partial NP-C1 phenotype in carriers. In the present study, we examined this possibility in heterozygotes of a natural loss-of-function mutant Npc1 mouse model. We found partial motor dysfunction and increased anxiety-like behavior in Npc1 +/-mice by 9 weeks of age.

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Section: Discussionmentioning

confidence: 98%

Neurological Dysfunction in Early Maturity of a Model for Niemann–Pick C1 Carrier Status

et al. 2016

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“…Also, Kv 3.1 is involved in regulating the duration and amplitude of the presynaptic potential, thus controlling evoked neurotransmitter release [40]. Given their essential role in modulating neuronal activity, reduction of Kv 3.1 channel expression and/or activity has been linked to neurodegenerative disorders such as Alzheimer’s disease [41], inherited ataxia [42, 43], schizophrenia [44] and intellectual disability [45]. Recently, a role of Kv 3.1 in causing a distinct form of progressive myoclonus epilepsy called myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK) has been described [46].…”

Section: Discussionmentioning

confidence: 99%

A Potassium-Selective Current Affected by Micromolar Concentrations of Anion Transport Inhibitors

Costa

Civello

Bernardinelli

et al. 2018

Cell Physiol Biochem

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Background/Aims: In the human genome, more than 400 genes encode ion channels, which are ubiquitously expressed and often coexist and participate in almost all physiological processes. Therefore, ion channel blockers represent fundamental tools in discriminating the contribution of individual channel types to a physiological phenomenon. However, unspecific effects of these compounds may represent a confounding factor. Three commonly used chloride channel inhibitors, i.e. 4,4′-diisothiocyano-2,2′-stilbene-disulfonic acid (DIDS), 5-nitro-2-[(3-phenylpropyl) amino]benzoic acid (NPPB) and the anti-inflammatory drug niflumic acid were tested to identify the lowest concentration effective on Cl^- channels and ineffective on K⁺ channels. Methods: The activity of the above mentioned compounds was tested by whole cell patch-clamp on the swelling-activated Cl^- current ICl,swell and on the endogenous voltage-dependent, outwardly rectifying K⁺ selective current in human kidney cell lines (HEK 293/HEK 293 Phoenix). Results: Micromolar (1-10 µM) concentrations of DIDS and NPPB could not discriminate between the Cl^- and K⁺ selective currents. Specifically, 1 µM DIDS only affected the K⁺ current and 10 µM NPPB equally affected the Cl^- and K⁺ currents. Only relatively high (0.1-1 mM) concentrations of DIDS and prolonged (5 minutes) exposure to 0.1-1 mM NPPB preferentially suppressed the Cl^- current. Niflumic acid preferentially inhibited the Cl^- current, but also significantly affected the K⁺ current. The endogenous voltage-dependent, outwardly rectifying K⁺ selective current in HEK 293/HEK 293 Phoenix cells was shown to arise from the Kv 3.1 channel, which is extensively expressed in brain and is involved in neurological diseases. Conclusion: The results of the present study underscore that sensitivity of a given physiological phenomenon to the Cl^- channel inhibitors NPPB, DIDS and niflumic acid may actually arise from an inhibition of Cl^- channels but can also result from an inhibition of voltage-dependent K⁺ channels, including the Kv 3.1 channel. The use of niflumic acid as anti-inflammatory drug in patients with concomitant Kv 3.1 dysfunction may result contraindicated.

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“…We examined the KIF5B distribution pattern in Kv3.1 KO mice, which were published previously (Ho et al, 1997;Sánchez et al, 2000;Hurlock et al, 2009). The KO mice were confirmed with western blotting and PCR-based genotyping (Fig.…”

Section: Kv31 Significantly Increases the Copy Number Of Kif5b-yfp Omentioning

confidence: 99%

“…Kv3.1 knockout (KO) mouse line was kindly provided by Dr R. Joho at UT Southwestern Medical Center and have been maintained using a PCR-based genotyping procedure as previously described (Ho et al, 1997;Sánchez et al, 2000;Hurlock et al, 2009). The Kv3.1 KO mice were backcrossed with BL6 for ten generations.…”

Section: Kv31 Knockout Mouse Genotypingmentioning

confidence: 99%

Activation of conventional kinesin motors in clusters by shaw voltage-gated potassium channels

Barry

et al. 2013

Journal of Cell Science

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SummaryThe conventional kinesin motor transports many different cargos to specific locations in neurons. How cargos regulate motor function remains unclear. Here we focus on KIF5, the heavy chain of conventional kinesin, and report that the Kv3 (Shaw) voltage-gated K + channel, the only known tetrameric KIF5-binding protein, clusters and activates KIF5 motors during axonal transport. Endogenous KIF5 often forms clusters along axons, suggesting a potential role of KIF5-binding proteins. Our biochemical assays reveal that the highaffinity multimeric binding between the Kv3.1 T1 domain and KIF5B requires three basic residues in the KIF5B tail. Kv3.1 T1 competes with the motor domain and microtubules, but not with kinesin light chain 1 (KLC1), for binding to the KIF5B tail. Live-cell imaging assays show that four KIF5-binding proteins, Kv3.1, KLC1 and two synaptic proteins SNAP25 and VAMP2, differ in how they regulate KIF5B distribution. Only Kv3.1 markedly increases the frequency and number of KIF5B-YFP anterograde puncta. Deletion of Kv3.1 channels reduces KIF5 clusters in mouse cerebellar neurons. Therefore, clustering and activation of KIF5 motors by Kv3 regulate the motor number in carrier vesicles containing the channel proteins, contributing not only to the specificity of Kv3 channel transport, but also to the cargo-mediated regulation of motor function.

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Rescue of Motor Coordination by Purkinje Cell-Targeted Restoration of Kv3.3 Channels inKcnc3-Null Mice RequiresKcnc1

Cited by 35 publications

References 49 publications

Neurological Dysfunction in Early Maturity of a Model for Niemann–Pick C1 Carrier Status

Neurological Dysfunction in Early Maturity of a Model for Niemann–Pick C1 Carrier Status

A Potassium-Selective Current Affected by Micromolar Concentrations of Anion Transport Inhibitors

Activation of conventional kinesin motors in clusters by shaw voltage-gated potassium channels

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