• 生物活性

靶点及简介 ：

GsMTx4 是一种蜘蛛毒液肽，选择性地抑制属于 Piezo 和 TRP 通道家族的阳离子可渗透的机械敏感性通道(MSCs)。GsMTx4 是一种重要的药理学工具，用于鉴定兴奋性 MSCs 在正常生理学和病理学中的作用。GsMTx4 显着减弱膀胱机能亢进。

GsMTx4是一种由34个氨基酸组成的蜘蛛毒素肽，属于huwentoxin-1家族[1]。GsMTx4选择性地抑制属于Piezo、TRPC1和TRPC6通道的阳离子渗透机械敏感通道（MSCs）。

GsMTx4是从蜘蛛毒液中分离出来的一种类似于许多其他通道活性肽的物质，它们都是建立在保守的抑制性半胱氨酸结（ICK）骨架上的小型（3-5 kD）两亲分子[4]。GsMTx4对于抑制机械敏感通道具有很高的效力，并且其抑制作用不具有立体特异性，即其左旋和右旋异构体均能够抑制MSCs[3]。

GsMTx4可以显著减轻膀胱过度活动[2]。已经证明，通过腹腔注射GsMTx-4可以减少由卡拉胶或坐骨神经损伤引起的机械性高敏感性[5]，但它不会抑制培养的DRG神经元中的SAC电流[6]。

GsMTx4是一种重要的药理学工具，用于确定这些兴奋性MSC在正常生理和病理中的作用[4]。

GsMTx4 is a 34 amino acid spider venom peptide and belongs to the huwentoxin-1 family[1]. GsMTx4 selectively inhibits cation-permeable mechanosensitive channels (MSCs) belonging to the Piezo, TRPC1 and TRPC6 channels.

GsMTx4 is similar to many other channel-active peptides isolated from spider venom, which are small (3–5 kD) amphipathic molecules built on a conserved inhibitory cysteine-knot (ICK) backbone[4].GsMTx4 has high potency for inhibiting mechanosensitive channels, and its inhibition is not stereospecific, i.e., both its enantiomers (L- and D-form) inhibiting MSCs[3].

GsMTx4 significantly attenuates bladder hyperactivity[2]. Intraperitoneal injection of GsMTx-4 has been shown to reduce mechanical hyperalgesia induced by carrageenan or sciatic nerve injury[5], although it does not inhibit SAC currents in cultured DRG neurons[6].

GsMTx4 is an important pharmacological tool for identifying the role of these excitatory MSCs in normal physiology and pathology[4].

• 验证及参考文献

参考文献：

[1]. Suchyna TM, et al. Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels. J Gen Physiol. 2000 May;115(5):583-98.

[2]. Liu Q, et al. Increased Piezo1 channel activity in interstitial Cajal-like cells induces bladder hyperactivity by functionally interacting with NCX1 in rats with cyclophosphamide-induced cystitis. Exp Mol Med. 2018 May 7;50(5):60.

[3]. Suchyna T.M., Tape S.E., Gottlieb P.A. Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers. Nature. 2004;430:235–240.

[4]. Gnanasambandam R, et al. GsMTx4: Mechanism of Inhibiting Mechanosensitive Ion Channels. Biophys J. 2017 Jan 10;112(1):31-45.

[5]. Park SP, et al. A tarantula spider toxin, GsMTx4, reduces mechanical and neuropathic pain. Pain. 2008;137:208–217.

[6]. Drew LJ, , et al.. High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain. PLoS ONE. 2007;2:e515.