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TPC2-A1-N

CAS No. : 136186-07-7

MCE 国际站：TPC2-A1-N

产品活性：TPC2-A1-N 是一种强大的 Ca²⁺-可渗透双孔通道 2 (TPC2) 的激动剂，通过模拟 NAADP 的生理作用发挥作用。TPC2-A1-N 可诱导 TPC2 显著的 Ca²⁺ 响应 (EC₅₀=7.8 μM)，这种响应并可被一些 TPC 阻断剂阻断。TPC2-A1-N 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  |  Neuronal Signaling

作用靶点：Calcium 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-N (10 μM) reproducibly evokes Ca²⁺ signals, and TPC2-A1-N response reachs its plateau faster than TPC2-A1-P. The EC₅₀ in full concentration-effect relationships for the plateau response is 7.8 μM for TPC2-A1-N in a cell line stably expressing TPC2^L11A/L12A.
TPC2-A1-N (10 μM) evokes Ca²⁺ influx through the TPC2 pore evokes Ca²⁺ signals in cells expressing TPC2L11A/L12A but not TPC2^{L11A/L12A/L265P}. Additionally, the responses to TPC2-A1-N can be selectively blocked by the identified TPC2 blockers Tetrandrine (HY-13764, Tet), Raloxifene (HY-13738, Ral), and Fluphenazine (HY-A0081, Flu) by removal of extracellular Ca²⁺.
In endo-lysosomal patch-clamp experiments, TPC2-A1-N (30 μM) elicits currents using Na⁺ as the major permeantion, in vacuolin-enlarged endo-lysosomes isolated from isolated from HEK293 cells transiently expressing human TPC2 (hTPC2) but not in cells expressing TPC1.
In endo-lysosomal patch-clamp experiments, TPC2-A1-N (30 μM) induces larger currents in endo-lysosomes isolated from cells expressing a gain-of-function variant of TPC2 (TPC2^M484L) compared to the wild-type isoform, and exhibits an EC₅₀ value of 0.6 μM for TPC2-A1-N.

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