CatSper and Two-Pore channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Abstract

CatSper channels (CatSper1-4, nomenclature as agreed by NC-IUPHAR [13]) 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 [21]. In mammals, CatSper subunits are structurally most closely related to individual domains of voltage-activated calcium channels (Ca_v) [36]. CatSper1 [36], CatSper2 [33] and CatSpers 3 and 4 [25, 19, 32], in common with a putative 2TM auxiliary CatSperβ protein [24] and two putative 1TM associated CatSperγ and CatSperδ proteins [42, 11], 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 [37].

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 [4]. TPC3 is also found on the plasma membrane and forms a voltage-activated, non-inactivating Na⁺ channel [5]. All the three TPCs are Na⁺-selective under whole-cell or whole-organelle patch clamp recording [44, 7, 6]. The channels may also conduct Ca²⁺ [29].