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TRP Channels in Regulation of Mineral Homeostasis
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TRP Channels in Regulation of Mineral Homeostasis

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 10103

Special Issue Editor

Dr. Vladimir Chubanov

E-Mail Website
Guest Editor
Walther Straub Institute of Pharmacology and Toxicology, LMU Munich, Germany
Interests: TRPM channels; channelopathies; magnesium homeostasis; drug screen; mouse genetic models

Special Issue Information

Dear Colleagues,

Zn2+, Mg2+, and Ca2+ are the most abundant divalent cations implicated in a plethora of physiological processes. The body's ability to tightly regulate the blood levels of Zn2+, Mg2+, and Ca2+ is essential for normal embryonic and postnatal development, and overall health. The circulation system contains less than 1% of these metal's total organismal content, and such a balance is orchestrated by intestinal absorption, renal excretion, and backup storage in bones and soft tissues. Accumulating evidence indicates that several members of the transient receptor potential (TRP) family of ion channels play s critical role in the homeostatic balance of Zn2+, Mg2+, and Ca2+ in a tissue-specific manner, including intestinal absorption (TRPV6, TRPM6, and TRPM7), renal reabsorption (TRPV5 and TRPM6), placental transport (TRPM6, TRPM7, and TRPV6), and storage in the bones (TRPV4 and TRPV5). Several known mutations in TRP channels are the molecular cause of inherited human diseases associated with the organismal deficiency of divalent cations. This Special Issue aims to highlight the recent advances in these research areas.

Dr. Vladimir Chubanov
Guest Editor

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Keywords

  • TRP channels
  • TRPM6
  • TRPM7
  • TRPV6
  • TRPV5
  • calcium
  • magnesium
  • zinc
  • sodium
  • trace metals
  • phosphate

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Published Papers (3 papers)

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Research

18 pages, 14503 KiB  
Article
A Pharmacokinetic and Metabolism Study of the TRPC6 Inhibitor SH045 in Mice by LC-MS/MS
by Xiao-Ning Chai, Friedrich-Alexander Ludwig, Anne Müglitz, Yuanyuan Gong, Michael Schaefer, Ralf Regenthal and Ute Krügel
Int. J. Mol. Sci. 2022, 23(7), 3635; https://doi.org/10.3390/ijms23073635 - 26 Mar 2022
Cited by 2 | Viewed by 2651
Abstract
TRPC6, the sixth member of the family of canonical transient receptor potential (TRP) channels, contributes to a variety of physiological processes and human pathologies. This study extends the knowledge on the newly developed TRPC6 blocker SH045 with respect to its main target organs [...] Read more.
TRPC6, the sixth member of the family of canonical transient receptor potential (TRP) channels, contributes to a variety of physiological processes and human pathologies. This study extends the knowledge on the newly developed TRPC6 blocker SH045 with respect to its main target organs beyond the description of plasma kinetics. According to the plasma concentration-time course in mice, SH045 is measurable up to 24 h after administration of 20 mg/kg BW (i.v.) and up to 6 h orally. The short plasma half-life and rather low oral bioavailability are contrasted by its reported high potency. Dosage limits were not worked out, but absence of safety concerns for 20 mg/kg BW supports further dose exploration. The disposition of SH045 is described. In particular, a high extravascular distribution, most prominent in lung, and a considerable renal elimination of SH045 were observed. SH045 is a substrate of CYP3A4 and CYP2A6. Hydroxylated and glucuronidated metabolites were identified under optimized LC-MS/MS conditions. The results guide a reasonable selection of dose and application route of SH045 for target-directed preclinical studies in vivo with one of the rare high potent and subtype-selective TRPC6 inhibitors available. Full article
(This article belongs to the Special Issue TRP Channels in Regulation of Mineral Homeostasis)
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16 pages, 3265 KiB  
Article
HIF-1α Dependent Upregulation of ZIP8, ZIP14, and TRPA1 Modify Intracellular Zn2+ Accumulation in Inflammatory Synoviocytes
by Noriyuki Hatano, Masaki Matsubara, Hiroka Suzuki, Yukiko Muraki and Katsuhiko Muraki
Int. J. Mol. Sci. 2021, 22(12), 6349; https://doi.org/10.3390/ijms22126349 - 14 Jun 2021
Cited by 14 | Viewed by 3047
Abstract
Intracellular free zinc ([Zn2+]i) is mobilized in neuronal and non-neuronal cells under physiological and/or pathophysiological conditions; therefore, [Zn2+]i is a component of cellular signal transduction in biological systems. Although several transporters and ion channels that carry [...] Read more.
Intracellular free zinc ([Zn2+]i) is mobilized in neuronal and non-neuronal cells under physiological and/or pathophysiological conditions; therefore, [Zn2+]i is a component of cellular signal transduction in biological systems. Although several transporters and ion channels that carry Zn2+ have been identified, proteins that are involved in Zn2+ supply into cells and their expression are poorly understood, particularly under inflammatory conditions. Here, we show that the expression of Zn2+ transporters ZIP8 and ZIP14 is increased via the activation of hypoxia-induced factor 1α (HIF-1α) in inflammation, leading to [Zn2+]i accumulation, which intrinsically activates transient receptor potential ankyrin 1 (TRPA1) channel and elevates basal [Zn2+]i. In human fibroblast-like synoviocytes (FLSs), treatment with inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1α), evoked TRPA1-dependent intrinsic Ca2+ oscillations. Assays with fluorescent Zn2+ indicators revealed that the basal [Zn2+]i concentration was significantly higher in TRPA1-expressing HEK cells and inflammatory FLSs. Moreover, TRPA1 activation induced an elevation of [Zn2+]i level in the presence of 1 μM Zn2+ in inflammatory FLSs. Among the 17 out of 24 known Zn2+ transporters, FLSs that were treated with TNF-α and IL-1α exhibited a higher expression of ZIP8 and ZIP14. Their expression levels were augmented by transfection with an active component of nuclear factor-κB P65 and HIF-1α expression vectors, and they could be abolished by pretreatment with the HIF-1α inhibitor echinomycin (Echi). The functional expression of ZIP8 and ZIP14 in HEK cells significantly increased the basal [Zn2+]i level. Taken together, Zn2+ carrier proteins, TRPA1, ZIP8, and ZIP14, induced under HIF-1α mediated inflammation can synergistically change [Zn2+]i in inflammatory FLSs. Full article
(This article belongs to the Special Issue TRP Channels in Regulation of Mineral Homeostasis)
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21 pages, 2823 KiB  
Article
Functional Expression of TRPV1 Ion Channel in the Canine Peripheral Blood Mononuclear Cells
by Joanna K. Bujak, Daria Kosmala, Kinga Majchrzak-Kuligowska and Piotr Bednarczyk
Int. J. Mol. Sci. 2021, 22(6), 3177; https://doi.org/10.3390/ijms22063177 - 20 Mar 2021
Cited by 3 | Viewed by 3361
Abstract
TRPV1, known as a capsaicin receptor, is the best-described transient receptor potential (TRP) ion channel. Recently, it was shown to be expressed by non-excitable cells such as lymphocytes. However, the data regarding the functional expression of the TRPV1 channel in the immune cells [...] Read more.
TRPV1, known as a capsaicin receptor, is the best-described transient receptor potential (TRP) ion channel. Recently, it was shown to be expressed by non-excitable cells such as lymphocytes. However, the data regarding the functional expression of the TRPV1 channel in the immune cells are often contradictory. In the present study, we performed a phylogenetical analysis of the canine TRP ion channels, we assessed the expression of TRPV1 in the canine peripheral blood mononuclear cells (PBMC) by qPCR and Western blot, and we determined the functionality of TRPV1 by whole-cell patch-clamp recordings and calcium assay. We found high expression of TRPV2, -M2, and -M7 in the canine PBMCs, while expression of TRPV1, -V4 and, -M5 was relatively low. We confirmed that TRPV1 is expressed on the protein level in the PBMC and it localizes in the plasma membrane. The whole-cell patch-clamp recording revealed that capsaicin application caused a significant increase in the current density. Similarly, the results from the calcium assay show a dose-dependent increase in intracellular calcium level in the presence of capsaicin that was partially abolished by capsazepine. Our study confirms the expression of TRPV1 ion channel on both mRNA and protein levels in the canine PBMC and indicates that the ion channel is functional. Full article
(This article belongs to the Special Issue TRP Channels in Regulation of Mineral Homeostasis)
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