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。
货号:ajcx14822
CAS:1209500-46-8
分子式:C185H279N49O45S6
分子量：4101.89
溶解度:H2O : 16.67 mg/mL
纯度：98%
存储：Store at -20°C
库存：现货

Background:

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].

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.

Protocol:

Cell experiment [1]:
Cell lines	HEK 293 cells
Preparation method	For Piezo1 channels, the extracellular solution contained 145 mM NaCl, 5 mM KCl, 3 mM MgCl2, 0.1 mM CaCl2, and 10 mM HEPES (pH 7.4). The pipette solution contained 133 mM CsCl, 10 mM HEPES (pH 7.4). The inhibition produced by application of GsMTx4 was followed by ～60 s of washout, followed by application of WT GsMTx4 as a control.
Reaction Conditions	5 μM GsMTx4, 40s
Applications	GsMTx4 is a spider venom peptide that inhibits cationic mechanosensitive channels (MSCs). A model placing GsMTx4 at the membrane surface, where it is stabilized by the lysines, and occupying a small fraction of the surface area in unstressed membranes. When applied tension reduces lateral pressure in the lipids, the peptides penetrate deeper acting as “area reservoirs” leading to partial relaxation of the outer monolayer, thereby reducing the effective magnitude of stimulus acting on the MSC gate.
Animal experiment [2]:
Animal models	Male C57BL/6 mice
Dosage form	To the WT and ClockΔ19/Δ19 mice, GsMTx4 or vehicle was administered via intraperitoneal injection (IP) at two different time-points, Z12- and ZT0-IP (higher and lower Piezo1 expression periods in the WT mice, respectively). The WT and ClockΔ19/Δ19 mice were injected with 0.75 (low dose-IP) or 1.5 mg/kg (high dose-IP) of GsMTx4 in 100 μL of distilled water.
Applications	VF decreased at ZT12-IP in WT mice only with high dose of GsMTx4 but showed no effects in ClockΔ19/Δ19 mice. GsMTx4 did not affect Uvol in both mice at ZT12-IP. A decrease in Uvol was observed in both mice at ZT0-IP; however, it was unrelated to GsMTx4-IP. The effects of GsMTx4 changed associated with the circadian clock and Piezo1 expression level.
参考文献: [1]. Gnanasambandam R, et al. GsMTx4: Mechanism of Inhibiting Mechanosensitive Ion Channels. Biophys J. 2017 Jan 10;112(1):31-45. [2]. Ihara, Tatsuya, et al. "Different effects of GsMTx4 on nocturia associated with the circadian clock and Piezo1 expression in mice."Life Sciences278 (2021): 119555.