Defective trafficking of Kv2.1 channels in MPTP-induced nigrostriatal degeneration

Ru Yi Chao, Chia Hui Cheng, Sheng-Nan Wu, Pei-chun Chen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Intracellular protein trafficking is tightly regulated, and improper trafficking might be the fundamental provocateur for human diseases including neurodegeneration. In neurons, protein trafficking to and from the plasma membrane affects synaptic plasticity. Voltage-gated potassium channel 2.1 (Kv2.1) is a predominant delayed rectifier potassium (K + ) current, and electrical activity patterns of dopamine (DA) neurons within the substantia nigra are generated and modulated by the orchestrated function of different ion channels. The pathological hallmark of Parkinson's disease (PD) is the progressive loss of these DA neurons, resulting in the degeneration of striatal dopaminergic terminals. However, whether trafficking of Kv2.1 channels contributes to PD remains unclear. In this study, we demonstrated that MPTP/MPP + increases the surface expression of the Kv2.1 channel and causes nigrostriatal degeneration by using a subchronic MPTP mouse model. The inhibition of the Kv2.1 channel by using a specific blocker, guangxitoxin-1E, protected nigrostriatal projections against MPTP/MPP + insult and thus facilitated the recovery of motor coordination. These findings highlight the importance of trafficking of Kv2.1 channels in the pathogenesis of PD. (Figure presented.).

Original languageEnglish
Pages (from-to)483-497
Number of pages15
JournalJournal of Neurochemistry
Volume144
Issue number4
DOIs
Publication statusPublished - 2018 Feb 1

Fingerprint

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Parkinson Disease
Dopaminergic Neurons
Protein Transport
Neurons
Voltage-Gated Potassium Channels
Corpus Striatum
Dopamine
Neuronal Plasticity
Substantia Nigra
Ion Channels
Potassium
Cell membranes
Cell Membrane
Plasticity
Proteins
Recovery

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

@article{09c37c6da50b4d95be5e723e386b078a,
title = "Defective trafficking of Kv2.1 channels in MPTP-induced nigrostriatal degeneration",
abstract = "Intracellular protein trafficking is tightly regulated, and improper trafficking might be the fundamental provocateur for human diseases including neurodegeneration. In neurons, protein trafficking to and from the plasma membrane affects synaptic plasticity. Voltage-gated potassium channel 2.1 (Kv2.1) is a predominant delayed rectifier potassium (K + ) current, and electrical activity patterns of dopamine (DA) neurons within the substantia nigra are generated and modulated by the orchestrated function of different ion channels. The pathological hallmark of Parkinson's disease (PD) is the progressive loss of these DA neurons, resulting in the degeneration of striatal dopaminergic terminals. However, whether trafficking of Kv2.1 channels contributes to PD remains unclear. In this study, we demonstrated that MPTP/MPP + increases the surface expression of the Kv2.1 channel and causes nigrostriatal degeneration by using a subchronic MPTP mouse model. The inhibition of the Kv2.1 channel by using a specific blocker, guangxitoxin-1E, protected nigrostriatal projections against MPTP/MPP + insult and thus facilitated the recovery of motor coordination. These findings highlight the importance of trafficking of Kv2.1 channels in the pathogenesis of PD. (Figure presented.).",
author = "Chao, {Ru Yi} and Cheng, {Chia Hui} and Sheng-Nan Wu and Pei-chun Chen",
year = "2018",
month = "2",
day = "1",
doi = "10.1111/jnc.14282",
language = "English",
volume = "144",
pages = "483--497",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "4",

}

Defective trafficking of Kv2.1 channels in MPTP-induced nigrostriatal degeneration. / Chao, Ru Yi; Cheng, Chia Hui; Wu, Sheng-Nan; Chen, Pei-chun.

In: Journal of Neurochemistry, Vol. 144, No. 4, 01.02.2018, p. 483-497.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Defective trafficking of Kv2.1 channels in MPTP-induced nigrostriatal degeneration

AU - Chao, Ru Yi

AU - Cheng, Chia Hui

AU - Wu, Sheng-Nan

AU - Chen, Pei-chun

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Intracellular protein trafficking is tightly regulated, and improper trafficking might be the fundamental provocateur for human diseases including neurodegeneration. In neurons, protein trafficking to and from the plasma membrane affects synaptic plasticity. Voltage-gated potassium channel 2.1 (Kv2.1) is a predominant delayed rectifier potassium (K + ) current, and electrical activity patterns of dopamine (DA) neurons within the substantia nigra are generated and modulated by the orchestrated function of different ion channels. The pathological hallmark of Parkinson's disease (PD) is the progressive loss of these DA neurons, resulting in the degeneration of striatal dopaminergic terminals. However, whether trafficking of Kv2.1 channels contributes to PD remains unclear. In this study, we demonstrated that MPTP/MPP + increases the surface expression of the Kv2.1 channel and causes nigrostriatal degeneration by using a subchronic MPTP mouse model. The inhibition of the Kv2.1 channel by using a specific blocker, guangxitoxin-1E, protected nigrostriatal projections against MPTP/MPP + insult and thus facilitated the recovery of motor coordination. These findings highlight the importance of trafficking of Kv2.1 channels in the pathogenesis of PD. (Figure presented.).

AB - Intracellular protein trafficking is tightly regulated, and improper trafficking might be the fundamental provocateur for human diseases including neurodegeneration. In neurons, protein trafficking to and from the plasma membrane affects synaptic plasticity. Voltage-gated potassium channel 2.1 (Kv2.1) is a predominant delayed rectifier potassium (K + ) current, and electrical activity patterns of dopamine (DA) neurons within the substantia nigra are generated and modulated by the orchestrated function of different ion channels. The pathological hallmark of Parkinson's disease (PD) is the progressive loss of these DA neurons, resulting in the degeneration of striatal dopaminergic terminals. However, whether trafficking of Kv2.1 channels contributes to PD remains unclear. In this study, we demonstrated that MPTP/MPP + increases the surface expression of the Kv2.1 channel and causes nigrostriatal degeneration by using a subchronic MPTP mouse model. The inhibition of the Kv2.1 channel by using a specific blocker, guangxitoxin-1E, protected nigrostriatal projections against MPTP/MPP + insult and thus facilitated the recovery of motor coordination. These findings highlight the importance of trafficking of Kv2.1 channels in the pathogenesis of PD. (Figure presented.).

UR - http://www.scopus.com/inward/record.url?scp=85040676529&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040676529&partnerID=8YFLogxK

U2 - 10.1111/jnc.14282

DO - 10.1111/jnc.14282

M3 - Article

C2 - 29265365

AN - SCOPUS:85040676529

VL - 144

SP - 483

EP - 497

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 4

ER -