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CatSper and Two-Pore channels (TPC) C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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CatSper channels (CatSper1-4, nomenclature as agreed by NC-IUPHAR [10]) are putative 6TM, voltage-gated, alkalinization-activated calcium permeant channels that are presumed to assemble as a tetramer of α-like subunits and mediate the current ICatSper [16]. In mammals, CatSper subunits are structurally most closely related to individual domains of voltage-activated calcium channels (Cav) [27]. CatSper1 [27], CatSper2 [26] and CatSpers 3 and 4 [15,20,25], in common with a putative 2TM auxiliary CatSperβ protein [19] and two putative 1TM associated CatSperγ and CatSperδ proteins [8,32], are restricted to the testis and localised to the principle piece of sperm tail. The novel cross-species CatSper channel inhibitor, RU1968, has been proposed as a useful tool to aid characterisation of native CatSper channels [28].

Two-pore channels (TPCs) are structurally related to CatSpers, CaVs and NaVs. TPCs have a 2x6TM structure with twice the number of TMs of CatSpers and half that of CaVs. There are three animal TPCs (TPC1-TPC3). Humans have TPC1 and TPC2, but not TPC3. TPC1 and TPC2 are localized in endosomes and lysosomes [2]. TPC3 is also found on the plasma membrane and forms a voltage-activated, non-inactivating Na+ channel [3]. All the three TPCs are Na+-selective under whole-cell or whole-organelle patch clamp recording [4-5,34]. The channels may also conduct Ca2+ [23].

Channels and Subunits

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Targets of relevance to immunopharmacology are highlighted in blue

CatSper1 C Show summary » More detailed page go icon to follow link

CatSper2 C Show summary » More detailed page go icon to follow link

CatSper3 C Show summary » More detailed page go icon to follow link

CatSper4 C Show summary » More detailed page go icon to follow link

TPC1 C Show summary » More detailed page go icon to follow link

TPC2 C Show summary » More detailed page go icon to follow link

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Further reading

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References

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NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation (select format):

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Mathie AA, Peters JA, Veale EL, Striessnig J, Kelly E, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Ion channels. Br J Pharmacol. 180 Suppl 2:S145-S222.