Role of dimer formation in modulating neuronal sodium channel properties
二聚体形成在调节神经元钠通道特性中的作用
基本信息
- 批准号:10741033
- 负责人:
- 金额:$ 42.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:Action PotentialsAddressAtaxiaBiochemicalBiological AssayBrainCellsDetectionDevelopmentDiseaseEnsureEpilepsyFutureGenerationsGoalsHumanInvestigationKnowledgeLeadLigationLinkMembraneMolecularMuscleMuscle CellsMutationMyotoniaNeuronsPainPathologicPharmacologyPhysiologicalPropertyProtein IsoformsProteinsReportingResearchResearch Project GrantsResistanceRoleSCN1A proteinSCN2A proteinSCN8A geneSignal TransductionSodiumSodium ChannelSpecificitySpinal GangliaSystemTEV proteaseTechnologyTestingTetrodotoxinTobacco useVariantWorkautism spectrum disorderdesigndesign and constructiondifopeindimerexcitatory neuronexperimental studyinhibitory neuronmutantnervous system disorderneuronal excitabilitynovelprotein protein interactionsodium channel proteinstreatment strategyvoltage
项目摘要
Summary/Abstract
Voltage-gated sodium channels are major contributors to the generation and propagation of action potentials in
neurons and muscle. Changes in the properties of sodium currents can substantially alter the excitability of
excitable cells. Indeed, sodium channel variants have been associated with a wide array of disorders of
excitability, including pain, epilepsy, ataxias, autism, myotonias and arrythmias. A multitude of sodium channel
disease mutations have been characterized. Many mutations can alter diverse sodium current properties and
the observed changes can range from profound to subtle. Interestingly, although many mutations have dominant
effects, the vast majority of characterizations have focused on isolated channel variants. Several recent studies
suggest that some voltage-gated sodium channels can form dimers and that dimer formation may alter the impact
of specific variants on sodium current properties. If dimer formation substantially alters sodium current properties
and/or the physiological consequences of disease mutations, then investigations of the functional consequences
of disease mutants in the presence of wild-type channels, other variants and even other isoforms may be needed
to fully understand how specific channel isoforms and variants contribute to electrogenesis and different
pathological conditions. We will investigate if dimer formation can result in changes in multiple properties,
including activation, deactivation, fast inactivation, slow inactivation and persistent currents of Nav1.1 and
Nav1.7 isoforms. Next, we will use Proximity Ligation Assays to examine the potential of dimer formation on
brain isoforms in cell systems. Finally, we will examine potential consequences of dimer formation on Nav1.6
and Nav1.7 channel variants associated with pain expressed in dorsal root ganglion neurons to help determine
if dimers can impact the properties of channels in a natural cell background. This exploratory research project
targets several key gaps in our knowledge relating to the potential consequences of VGSC dimers. A fuller
understanding of this phenomena could lead to a more complete understanding of channelopathies and possibly
spur the development of novel treatment strategies.
摘要/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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THEODORE R CUMMINS其他文献
THEODORE R CUMMINS的其他文献
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{{ truncateString('THEODORE R CUMMINS', 18)}}的其他基金
Harnessing gating-pore currents to identify novel Nav1.7 modulators
利用门孔电流识别新型 Nav1.7 调制器
- 批准号:
8321973 - 财政年份:2011
- 资助金额:
$ 42.76万 - 项目类别:
Harnessing gating-pore currents to identify novel Nav1.7 modulators
利用门孔电流识别新型 Nav1.7 调制器
- 批准号:
8259349 - 财政年份:2011
- 资助金额:
$ 42.76万 - 项目类别:
Development of isoform specific sensory neuronal sodium channel blockers
异构体特异性感觉神经元钠通道阻滞剂的开发
- 批准号:
7212747 - 财政年份:2007
- 资助金额:
$ 42.76万 - 项目类别:
Development of isoform specific sensory neuronal sodium channel blockers
异构体特异性感觉神经元钠通道阻滞剂的开发
- 批准号:
7346915 - 财政年份:2007
- 资助金额:
$ 42.76万 - 项目类别:
Sodium channels and electrogenesis in sensory neurons
感觉神经元中的钠通道和电发生
- 批准号:
9083374 - 财政年份:2006
- 资助金额:
$ 42.76万 - 项目类别:
Sodium channels and electrogenesis in sensory neurons
感觉神经元中的钠通道和电发生
- 批准号:
9750827 - 财政年份:2006
- 资助金额:
$ 42.76万 - 项目类别:
Sodium channels and electrogenesis in sensory neurons
感觉神经元中的钠通道和电发生
- 批准号:
7744613 - 财政年份:2006
- 资助金额:
$ 42.76万 - 项目类别:
Sodium channels and electrogenesis in sensory neurons
感觉神经元中的钠通道和电发生
- 批准号:
8504397 - 财政年份:2006
- 资助金额:
$ 42.76万 - 项目类别:
Sodium channels and electrogenesis in sensory neurons
感觉神经元中的钠通道和电发生
- 批准号:
8288069 - 财政年份:2006
- 资助金额:
$ 42.76万 - 项目类别:
Sodium channels and electrogenesis in sensory neurons
感觉神经元中的钠通道和电发生
- 批准号:
7014693 - 财政年份:2006
- 资助金额:
$ 42.76万 - 项目类别:
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