TRPC1 as a negative regulator for TRPC4 and TRPC5 channels

Kim, Jinsung; Ko, Jung Hwa; Myeong, Jongyun; Kwak, Misun; Hong, Chansik; So, Insuk

doi:10.1007/s00424-019-02289-w

Cited by 22 publications

(22 citation statements)

References 61 publications

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“…The authors suggested that the cause was reduced interaction with the SOCE modulator stromal interaction molecule 1 (STIM1) and decreased Ca 2+ entry into the cell. However, our recent study showed that TRPC1 functions as a negative regulator of TRPC4 and TRPC5 (Figure 2C; Kim et al, 2019). Heterodimers FIGURE 1 | Summary of TRP studies using knockout mice or antagonists to investigate therapeutic targets of neurodegenerative diseases.…”

Section: Trpc1mentioning

confidence: 99%

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases

et al. 2020

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The development of treatment for neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis is facing medical challenges due to the increasingly aging population. However, some pharmaceutical companies have ceased the development of therapeutics for NDs, and no new treatments for NDs have been established during the last decade. The relationship between ND pathogenesis and risk factors has not been completely elucidated. Herein, we review the potential involvement of transient receptor potential (TRP) channels in NDs, where oxidative stress and disrupted Ca 2+ homeostasis consequently lead to neuronal apoptosis. Reactive oxygen species (ROS) -sensitive TRP channels can be key risk factors as polymodal sensors, since progressive late onset with secondary pathological damage after initial toxic insult is one of the typical characteristics of NDs. Recent evidence indicates that the dysregulation of TRP channels is a missing link between disruption of Ca 2+ homeostasis and neuronal loss in NDs. In this review, we discuss the latest findings regarding TRP channels to provide insights into the research and quests for alternative therapeutic candidates for NDs. As the structures of TRP channels have recently been revealed by cryo-electron microscopy, it is necessary to develop new TRP channel antagonists and reevaluate existing drugs.

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Section: Trpc1mentioning

confidence: 99%

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases

et al. 2020

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“…One of the most fascinating features of TRPC4 and TRPC5 channels is the shape of I-V curve [34]. In physiological membrane potential (−90 mV to 40 mV), the I-V curves of both channels mimic the inward rectifier, such as inwardly-rectifying potassium channels.…”

Section: Rectificationmentioning

confidence: 99%

“…In other words, heteromeric TRPC1/4 or TRPC1/5 channels show outwardly-rectifying I-V curves. An extensive review regarding electrophysiological difference between homomeric and heteromeric channels can be found elsewhere [2,3,34,62].…”

Section: Rectificationmentioning

confidence: 99%

“…Classically, TRPC4 and 5 channels are known to be activated by G-proteins and their downstream signal transduction pathways, such as Gq-PLC pathway [2,3,21,22,34,35]. Intensive researches have been done on delineating functional relationship among TRPC4, 5 channels and phosphatidylinositol 4,5-bisphosphate (PIP 2 ) [36][37][38][39][40][41][42], intracellular Ca 2+ ([Ca 2+ ] i ) and protein kinase C (PKC) [43,44].…”

Section: Introductionmentioning

confidence: 99%

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Structure–Function Relationship and Physiological Roles of Transient Receptor Potential Canonical (TRPC) 4 and 5 Channels

Kim

Hong

et al. 2019

Cells

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The study of the structure–function relationship of ion channels has been one of the most challenging goals in contemporary physiology. Revelation of the three-dimensional (3D) structure of ion channels has facilitated our understanding of many of the submolecular mechanisms inside ion channels, such as selective permeability, voltage dependency, agonist binding, and inter-subunit multimerization. Identifying the structure–function relationship of the ion channels is clinically important as well since only such knowledge can imbue potential therapeutics with practical possibilities. In a sense, recent advances in the understanding of the structure–relationship of transient receptor potential canonical (TRPC) channels look promising since human TRPC channels are calcium-permeable, non-selective cation channels expressed in many tissues such as the gastrointestinal (GI) tract, kidney, heart, vasculature, and brain. TRPC channels are known to regulate GI contractility and motility, pulmonary hypertension, right ventricular hypertrophy, podocyte injury, seizure, fear, anxiety-like behavior, and many others. In this article, we tried to elaborate recent findings of Cryo-EM (cryogenic-electron microscopy) based structural information of TRPC 4 and 5 channels and domain-specific functions of the channel, such as G-protein mediated activation mechanism, extracellular modification of the channel, homo/hetero-tetramerization, and pharmacological gating mechanisms.

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“…However, in the adult brain, TRPC1 forms complexes with TRPC4 and TRPC5, but not with group 3 isoforms [8][9][10]. Heterologous co-expression of TRPC1 with TRPC4 or TRPC5 leads to channels with strongly modified functional properties compared to TRPC4 and TRPC5 homomers [5,7,[11][12][13]. These include changes in the shape of the current-voltage (IV) relationship and a reduction in Ca 2+ permeability.…”

Section: Introductionmentioning

confidence: 99%

TRPC1 Regulates the Activity of a Voltage-Dependent Nonselective Cation Current in Hippocampal CA1 Neurons

Kepura

Braun

Dietrich

et al. 2020

Cells

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The cation channel subunit TRPC1 is strongly expressed in central neurons including neurons in the CA1 region of the hippocampus where it forms complexes with TRPC4 and TRPC5. To investigate the functional role of TRPC1 in these neurons and in channel function, we compared current responses to group I metabotropic glutamate receptor (mGluR I) activation and looked for major differences in dendritic morphology in neurons from TRPC1+/+ and TRPC1−/− mice. mGluR I stimulation resulted in the activation of a voltage-dependent nonselective cation current in both genotypes. Deletion of TRPC1 resulted in a modification of the shape of the current-voltage relationship, leading to an inward current increase. In current clamp recordings, the percentage of neurons that responded to depolarization in the presence of an mGluR I agonist with a plateau potential was increased in TRPC1−/− mice. There was also a small increase in the minor population of CA1 neurons that have more than one apical dendrite in TRPC1−/− mice. We conclude that TRPC1 has an inhibitory effect on receptor-operated nonselective cation channels in hippocampal CA1 neurons probably as a result of heterotetramer formation with other TRPC isoforms, and that TRPC1 deletion has only minor effects on dendritic morphology.

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TRPC1 as a negative regulator for TRPC4 and TRPC5 channels

Cited by 22 publications

References 61 publications

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases

Structure–Function Relationship and Physiological Roles of Transient Receptor Potential Canonical (TRPC) 4 and 5 Channels

TRPC1 Regulates the Activity of a Voltage-Dependent Nonselective Cation Current in Hippocampal CA1 Neurons

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