CatSper and Two-Pore channels (TPC) in GtoPdb v.2022.1

Abstract

CatSper channels (CatSper1-4, nomenclature as agreed by NC-IUPHAR [14]) 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 I_CatSper [23]. In mammals, CatSper subunits are structurally most closely related to individual domains of voltage-activated calcium channels (Ca_v) [40]. CatSper1 [40], CatSper2 [37] and CatSpers 3 and 4 [27, 21, 36], in common with a putative 2TM auxiliary CatSperβ protein [26] and two putative 1TM associated CatSperγ and CatSperδ proteins [46, 12], 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 [41].

Two-pore channels (TPCs) are structurally related to CatSpers, Ca_Vs and Na_Vs. TPCs have a 2x6TM structure with twice the number of TMs of CatSpers and half that of Ca_Vs. There are three animal TPCs (TPC1-TPC3). Humans have TPC1 and TPC2, but not TPC3. TPC1 and TPC2 are localized in endosomes and lysosomes [5]. TPC3 is also found on the plasma membrane and forms a voltage-activated, non-inactivating Na⁺ channel [6]. All the three TPCs are Na⁺-selective under whole-cell or whole-organelle patch clamp recording [48, 8, 7]. The channels may also conduct Ca²⁺ [31].