The T-type calcium channelosome

Weiss, Norbert; Zamponi, Gerald W.

doi:10.1007/s00424-023-02891-z

Cited by 5 publications

(1 citation statement)

References 175 publications

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“…Among other studies, Cav2 channels were found to be embedded into protein networks containing around ∼200 proteins [ 25 ], including ion channels, transporters, G-protein-coupled receptor-mediated signaling, and the release machinery of synaptic vesicles. More recently, the T-type Cav channel interactome [ 26 ] was depicted as a “T-type calcium channelosome”.…”

Section: Introductionmentioning

confidence: 99%

High-Resolution Proteomics Unravel a Native Functional Complex of Cav1.3, SK3, and Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in Midbrain Dopaminergic Neurons

Belghazi,

Iborra,

Toutendji

et al. 2024

Cells

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Pacemaking activity in substantia nigra dopaminergic neurons is generated by the coordinated activity of a variety of distinct somatodendritic voltage- and calcium-gated ion channels. We investigated whether these functional interactions could arise from a common localization in macromolecular complexes where physical proximity would allow for efficient interaction and co-regulations. For that purpose, we immunopurified six ion channel proteins involved in substantia nigra neuron autonomous firing to identify their molecular interactions. The ion channels chosen as bait were Cav1.2, Cav1.3, HCN2, HCN4, Kv4.3, and SK3 channel proteins, and the methods chosen to determine interactions were co-immunoprecipitation analyzed through immunoblot and mass spectrometry as well as proximity ligation assay. A macromolecular complex composed of Cav1.3, HCN, and SK3 channels was unraveled. In addition, novel potential interactions between SK3 channels and sclerosis tuberous complex (Tsc) proteins, inhibitors of mTOR, and between HCN4 channels and the pro-degenerative protein Sarm1 were uncovered. In order to demonstrate the presence of these molecular interactions in situ, we used proximity ligation assay (PLA) imaging on midbrain slices containing the substantia nigra, and we could ascertain the presence of these protein complexes specifically in substantia nigra dopaminergic neurons. Based on the complementary functional role of the ion channels in the macromolecular complex identified, these results suggest that such tight interactions could partly underly the robustness of pacemaking in dopaminergic neurons.

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Section: Introductionmentioning

confidence: 99%

High-Resolution Proteomics Unravel a Native Functional Complex of Cav1.3, SK3, and Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in Midbrain Dopaminergic Neurons

Belghazi,

Iborra,

Toutendji

et al. 2024

Cells

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Silencing of the T-type voltage-gated calcium channel α1 subunit by fungus-mediated RNAi altered the structure of F-actin and caused defective behaviors in Ditylenchus destructor

Yang,

Zhou,

Yang

et al. 2024

Mol Biol Rep

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Kurarinone, a Lavandulyl Flavanone from Sophora flavescens, Inhibits T-type Calcium Channels and Exerts Analgesic Effects in a Mouse Model of Inflammatory Pain

Ali,

Choi,

Huang

et al. 2024

ACS Food Sci. Technol.

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Kurarinone, the major lavandulyl flavanone identified in the roots of Sophora flavescens, has been reported to have different channel and transporter activity modulation capacities; nevertheless, its ability to block T-type channels and inflammatory pain activity have not been fully investigated. In this work, we used the whole-cell patch clamp technique to examine the ability of kurarinone to block T-type calcium channels. Kurarinone acted as a nonselective T-type channel antagonist that inhibited Cav3.2 channels expressed in tsA-201 cells with an IC 50 of 1.1 ± 0.3 μM and blocked native T-type channels in mouse dorsal root ganglion neurons. Transiently expressed Cav2.2 channels were also blocked. Molecular docking analysis predicted that the phenyl ring, lavandulyl, and hydroxyl groups of kurarinone interact directly with the pore domains of all three T-type calcium channels via hydrogen and hydrophobic interactions. Kurarinone administered intraperitoneally (10 mg/kg/i.p.) significantly inhibited phase II of formalin-induced nocifensive responses in mice. Furthermore, kurarinone reduced thermal hyperalgesia and mechanical hypersensitivity in mice injected with Complete Freund's adjuvant (CFA) into the hind paw in an inflammatory pain mouse model. Taken together, our findings indicate that kurarinone has analgesic activity through blocking calcium channels.

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The T-type calcium channelosome

Cited by 5 publications

References 175 publications

High-Resolution Proteomics Unravel a Native Functional Complex of Cav1.3, SK3, and Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in Midbrain Dopaminergic Neurons

High-Resolution Proteomics Unravel a Native Functional Complex of Cav1.3, SK3, and Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in Midbrain Dopaminergic Neurons

Silencing of the T-type voltage-gated calcium channel α1 subunit by fungus-mediated RNAi altered the structure of F-actin and caused defective behaviors in Ditylenchus destructor

Kurarinone, a Lavandulyl Flavanone from Sophora flavescens, Inhibits T-type Calcium Channels and Exerts Analgesic Effects in a Mouse Model of Inflammatory Pain

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