Growth factors differentially regulate neuronal Cav channels via ERK-dependent signalling

A. J. Woodall; M. A. Richards; D. J. Turner; E. M. Fitzgerald

doi:10.1016/j.ceca.2007.10.001

Growth factors differentially regulate neuronal Cav channels via ERK-dependent signalling

A. J. Woodall, M. A. Richards, D. J. Turner, E. M. Fitzgerald

Research output: Contribution to journal › Article › peer-review

Abstract

Voltage-gated calcium channels (Cav) are tonically up-regulated via Ras/extracellular signal-regulated kinase (ERK) signalling in sensory neurones. However, the mechanisms underlying the specificity of cellular response to this pathway remain unclear. Neurotrophic factors are attractive candidates to be involved in this process as they are key regulators of ERK signalling and have important roles in neuronal survival, development and plasticity. Here, we report that in rat dorsal root ganglion neurones, endogenous nerve growth factor (NGF), glial derived neurotrophic factor (GDNF) and epidermal growth factor (EGF) are all involved in tonic ERK-dependent up-regulation of Cav channels. Chronic (overnight) deprivation of growth factors inhibits total Cav current according to developmental changes in expression of the cell surface receptors for NGF, GDNF and EGF. Whilst EGF specifically regulates transcriptional expression of Cavs, NGF and GDNF also acutely modulate Cav channels within a rapid (∼10 min) time-frame. These acute effects likely involve changes in the biophysical properties of Cavs, including altered channel gating rather than changes in surface expression. Furthermore, NGF, GDNF and EGF differentially regulate specific populations of Cavs. Thus, ERK-dependent regulation of Cav activity provides an elegant and extremely flexible system with which to tailor calcium influx to discrete functional demands. Crown Copyright © 2007.

Original language	English
Pages (from-to)	562-575
Number of pages	13
Journal	Cell calcium
Volume	43
Issue number	6
DOIs	https://doi.org/10.1016/j.ceca.2007.10.001
Publication status	Published - Jun 2008

Keywords

EGF
GDNF
Ion channel modulation
MAPK
NGF
Patch-clamp
Sensory neurones
Voltage-gated calcium channels

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10.1016/j.ceca.2007.10.001

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title = "Growth factors differentially regulate neuronal Cav channels via ERK-dependent signalling",

abstract = "Voltage-gated calcium channels (Cav) are tonically up-regulated via Ras/extracellular signal-regulated kinase (ERK) signalling in sensory neurones. However, the mechanisms underlying the specificity of cellular response to this pathway remain unclear. Neurotrophic factors are attractive candidates to be involved in this process as they are key regulators of ERK signalling and have important roles in neuronal survival, development and plasticity. Here, we report that in rat dorsal root ganglion neurones, endogenous nerve growth factor (NGF), glial derived neurotrophic factor (GDNF) and epidermal growth factor (EGF) are all involved in tonic ERK-dependent up-regulation of Cav channels. Chronic (overnight) deprivation of growth factors inhibits total Cav current according to developmental changes in expression of the cell surface receptors for NGF, GDNF and EGF. Whilst EGF specifically regulates transcriptional expression of Cavs, NGF and GDNF also acutely modulate Cav channels within a rapid (∼10 min) time-frame. These acute effects likely involve changes in the biophysical properties of Cavs, including altered channel gating rather than changes in surface expression. Furthermore, NGF, GDNF and EGF differentially regulate specific populations of Cavs. Thus, ERK-dependent regulation of Cav activity provides an elegant and extremely flexible system with which to tailor calcium influx to discrete functional demands. Crown Copyright {\textcopyright} 2007.",

keywords = "EGF, GDNF, Ion channel modulation, MAPK, NGF, Patch-clamp, Sensory neurones, Voltage-gated calcium channels",

author = "Woodall, {A. J.} and Richards, {M. A.} and Turner, {D. J.} and Fitzgerald, {E. M.}",

year = "2008",

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T1 - Growth factors differentially regulate neuronal Cav channels via ERK-dependent signalling

AU - Woodall, A. J.

AU - Richards, M. A.

AU - Turner, D. J.

AU - Fitzgerald, E. M.

PY - 2008/6

Y1 - 2008/6

N2 - Voltage-gated calcium channels (Cav) are tonically up-regulated via Ras/extracellular signal-regulated kinase (ERK) signalling in sensory neurones. However, the mechanisms underlying the specificity of cellular response to this pathway remain unclear. Neurotrophic factors are attractive candidates to be involved in this process as they are key regulators of ERK signalling and have important roles in neuronal survival, development and plasticity. Here, we report that in rat dorsal root ganglion neurones, endogenous nerve growth factor (NGF), glial derived neurotrophic factor (GDNF) and epidermal growth factor (EGF) are all involved in tonic ERK-dependent up-regulation of Cav channels. Chronic (overnight) deprivation of growth factors inhibits total Cav current according to developmental changes in expression of the cell surface receptors for NGF, GDNF and EGF. Whilst EGF specifically regulates transcriptional expression of Cavs, NGF and GDNF also acutely modulate Cav channels within a rapid (∼10 min) time-frame. These acute effects likely involve changes in the biophysical properties of Cavs, including altered channel gating rather than changes in surface expression. Furthermore, NGF, GDNF and EGF differentially regulate specific populations of Cavs. Thus, ERK-dependent regulation of Cav activity provides an elegant and extremely flexible system with which to tailor calcium influx to discrete functional demands. Crown Copyright © 2007.

AB - Voltage-gated calcium channels (Cav) are tonically up-regulated via Ras/extracellular signal-regulated kinase (ERK) signalling in sensory neurones. However, the mechanisms underlying the specificity of cellular response to this pathway remain unclear. Neurotrophic factors are attractive candidates to be involved in this process as they are key regulators of ERK signalling and have important roles in neuronal survival, development and plasticity. Here, we report that in rat dorsal root ganglion neurones, endogenous nerve growth factor (NGF), glial derived neurotrophic factor (GDNF) and epidermal growth factor (EGF) are all involved in tonic ERK-dependent up-regulation of Cav channels. Chronic (overnight) deprivation of growth factors inhibits total Cav current according to developmental changes in expression of the cell surface receptors for NGF, GDNF and EGF. Whilst EGF specifically regulates transcriptional expression of Cavs, NGF and GDNF also acutely modulate Cav channels within a rapid (∼10 min) time-frame. These acute effects likely involve changes in the biophysical properties of Cavs, including altered channel gating rather than changes in surface expression. Furthermore, NGF, GDNF and EGF differentially regulate specific populations of Cavs. Thus, ERK-dependent regulation of Cav activity provides an elegant and extremely flexible system with which to tailor calcium influx to discrete functional demands. Crown Copyright © 2007.

KW - EGF

KW - GDNF

KW - Ion channel modulation

KW - MAPK

KW - NGF

KW - Patch-clamp

KW - Sensory neurones

KW - Voltage-gated calcium channels

U2 - 10.1016/j.ceca.2007.10.001

DO - 10.1016/j.ceca.2007.10.001

M3 - Article

SN - 1532-1991

VL - 43

SP - 562

EP - 575

JO - Cell calcium

JF - Cell calcium

IS - 6

ER -

Growth factors differentially regulate neuronal Cav channels via ERK-dependent signalling

Abstract

Keywords

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