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TPC2-A1-P

CAS No. :

MCE 国际站：TPC2-A1-P

产品活性：TPC2-A1-P 是一种强大的膜渗透性的双孔通道 2 (TPC2) 激动剂 (EC₅₀=10.5 μM)，它通过模仿 PI(3,5)P2 的生理作用发挥作用。与 TPC2-A1-N (HY-131614) 相比，TPC2-A1-P 具有更高的诱导 Na⁺ 活化的能力，可用于检测完整细胞中 TPC2 通道的不同功能。

研究领域：Membrane Transporter/Ion Channel

作用靶点：Sodium Channel

In Vitro: Two-pore channels (TPC1-3) are ancient members of the voltage-gated ion channel superfamily. TPCs are expressed throughout the endo-lysosomal system and regulates the trafficking of various cargoes.
TPC2 can mediate different physiological and possibly pathophysiological effects depending on how it is activated. The ion selectivity of TPC2 is not fixed but rather agonist-dependent. TPC2 is a unique example of an ion channel that conducts different ions in response to different activating ligands.
TPC2-A1-P (10 μM) reproducibly evokes Ca²⁺ signals, and TPC2-A1-P response reachs its plateau slower than TPC2-A1-N (HY-131614). The EC₅₀ in full concentration-effect relationships for the plateau response is 10.5 μM for TPC2-A1-P in a cell line stably expressing TPC2^L11A/L12A.
TPC2-A1-P (10-30 μM) induces Ca²⁺ signals in Hela cells expressing TPC2 in the presence but not absence of extracellular Ca²⁺. However, the responses are smaller and delayed compared to TPC2-A1-N (HY-131614), consistent with the results obtained in cells stably expressing TPC2^L11A/L12A. TPC2-A1-P fails to induce Ca²⁺ signals in cells expressing ‘pore-dead’ TPC2^{L11A/L12A/L265P} and also fails to evoke Ca²⁺ signals in cells expressing human TRPML1 re-routed to the plasma membrane (TRPML1^ΔNC).
In endo-lysosomal patch-clamp experiments, TPC2-A1-P (10 μM) evokes currents in endo-lysosomes isolated from cells expressing TPC2 and TPC2^M484L, the currents evoked by TPC2-A1-P are significantly larger than those evoked by TPC2-A1-N (HY-131614) in both wild-type and gain-of-function variant,and exhibits an EC₅₀ value of 0.6 μM for TPC2-A1-P.

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