Iberiotoxin (trifluoroacetate salt) is a selective high conductance high conductance Ca2+-activated K+ channel inhibitor with a Kd of ~1 nM. Iberiotoxin (trifluoroacetate salt) does not block other types of voltage-dependent ion channels[1，2，3].
Iberiotoxin (trifluoroacetate salt) treatment affects rat mesenchymal stem cells (rMSCs) migration in the absence of platelet lysate (PL) by inducing a decrease in cell migration. 10 nM of Iberiotoxin (trifluoroacetate salt) abolishes the PL-induced migration effect on MSCs[3]. Iberiotoxin (trifluoroacetate salt) reversibly blocks Ca2+-activated K+ channel in excised membrane patches from bovine aortic smooth muscle. Iberiotoxin (trifluoroacetate salt) acts exclusively at the outer face of the channel and functions with IC50 values of about 250 pM[1].
Male Wistar rats (6-7 weeks old) with chronic heart failure (CHF), after perfusion of Iberiotoxin (trifluoroacetate salt), right ventricular weight/body weight and lung weight/body weight ratio as well as left ventricular end-diastolic diameter were increased and left ventricular ejection fraction was decreased, the sympathetic driving indexes was increased in sham rats, changes of these parameters further aggravated in CHF rats. In rats, Downregulation and blunted function of BKCa by Iberiotoxin (trifluoroacetate salt) in PVN may contribute to sympathoexcitation and deterioration of cardiac function in rats with chronic heart failure[4].BK channels were expressed in mouse lymphatic smooth muscle and Iberiotoxin (trifluoroacetate salt) (BK channel inhibitors) produced right-ward shifts in NONOate concentration-response curves[5].BKCa channels localize to the mitochondria of adult mouse[6], rat ventricular cardiomyocytes present and plasma membrane of neonatal cardiomyocytes,Inhibition of BKCa channels by Iberiotoxin (trifluoroacetate salt) protects neonatal hearts against myocardial ischemia and reperfusion injury[7]. Iberiotoxin (trifluoroacetate salt) as a blocker of KCa1.1 channels, inhibited acetylcholine relaxation in corpus cavernosum from db/+ mice, while there was no effect in tissue from db/db mice[8].
References:
[1]: Galvez A, Gimenez-Gallego G, et,al. Purification and characterization of a unique, potent, peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Buthus tamulus. J Biol Chem. 1990 Jul 5;265(19):11083-90. PMID: 1694175.
[2]: Echeverry S, Grismaldo A, et,al. Activation of BK Channel Contributes to PL-Induced Mesenchymal Stem Cell Migration. Front Physiol. 2020 Mar 24;11:210. doi: 10.3389/fphys.2020.00210. PMID: 32265729; PMCID: PMC7105713.
[3]: Candia S, Garcia ML, et,al. Mode of action of iberiotoxin, a potent blocker of the large conductance Ca(2+)-activated K+ channel. Biophys J. 1992 Aug;63(2):583-90. doi: 10.1016/S0006-3495(92)81630-2. PMID: 1384740; PMCID: PMC1262182.
[4]: Wang RJ, Wen ML, et,al. [Downregulation of large conductance calcium-activated potassium channels in paraventricular nucleus contributes to sympathoexcitation in rats with chronic heart failure]. Zhonghua Xin Xue Guan Bing Za Zhi. 2018 Mar 24;46(3):178-186. Chinese. doi: 10.3760/cma.j.issn.0253-3758.2018.03.003. PMID: 29562421.
[5]: Kim HJ, Li M, et,al. Large-conductance calcium-activated K+ channels, rather than KATP channels, mediate the inhibitory effects of nitric oxide on mouse lymphatic pumping. Br J Pharmacol. 2021 Oct;178(20):4119-4136. doi: 10.1111/bph.15602. Epub 2021 Aug 7. PMID: 34213021.
[6]: Frankenreiter S, Bednarczyk P, et,al. cGMP-Elevating Compounds and Ischemic Conditioning Provide Cardioprotection Against Ischemia and Reperfusion Injury via Cardiomyocyte-Specific BK Channels. Circulation. 2017 Dec 12;136(24):2337-2355. doi: 10.1161/CIRCULATIONAHA.117.028723. Epub 2017 Oct 19. PMID: 29051185.
[7]: Sanghvi S, Szteyn K, et,al. Inhibition of BKCa channels protects neonatal hearts against myocardial ischemia and reperfusion injury. Cell Death Discov. 2022 Apr 7;8(1):175. doi: 10.1038/s41420-022-00980-z. PMID: 35393410; PMCID: PMC8989942.
[8]: Comerma-Steffensen S, Prat-Duran J, et,al. Erectile Dysfunction and Altered Contribution of KCa1.1 and KCa2.3 Channels in the Penile Tissue of Type-2 Diabetic db/db Mice. J Sex Med. 2022 May;19(5):697-710. doi: 10.1016/j.jsxm.2022.02.021. Epub 2022 Mar 20. PMID: 35321830.
Iberiotoxin（三氟乙酸盐）是一种选择性高电导高电导 Ca2+- 激活的 K+ 通道抑制剂,Kd 约为 1 nM。 Iberiotoxin（三氟乙酸盐）不阻断其他类型的电压依赖性离子通道[1,2,3]。
Iberiotoxin（三氟乙酸盐）处理通过诱导细胞迁移减少,在没有血小板裂解物 (PL) 的情况下影响大鼠间充质干细胞 (rMSC) 的迁移。 10 nM 伊比利亚毒素（三氟乙酸盐）消除了 PL 诱导的 MSCs 迁移效应[3]。 Iberiotoxin（三氟乙酸盐）可逆地阻断牛主动脉平滑肌切除膜片中的 Ca2+- 激活的 K+ 通道。 Iberiotoxin（三氟乙酸盐）仅作用于通道的外表面,IC50 值约为 250 pM[1]。
患有慢性心力衰竭 (CHF) 的雄性 Wistar 大鼠（6-7 周龄）,灌注伊比利亚毒素（三氟醋酸盐）后,右心室重量/体重和肺重量/体重比以及左心室终末期 -舒张期直径增加,左心室射血分数降低,假大鼠的交感神经驱动指数增加,这些参数的变化在 CHF 大鼠中进一步加剧。在大鼠中,伊比利亚毒素（三氟乙酸盐）在 PVN 中下调和减弱 BKCa 的功能可能导致慢性心力衰竭大鼠的交感神经兴奋和心功能恶化[4]。BK 通道在小鼠淋巴管中表达平滑肌和 Iberiotoxin（三氟乙酸盐）（BK 通道抑制剂）使 NONOate 浓度-响应曲线向右移动[5]。BKCa 通道定位于成年小鼠的线粒体[6] ,存在大鼠心室心肌细胞和新生心肌细胞质膜,伊比利亚毒素（三氟乙酸盐）抑制 BKCa 通道可保护新生儿心脏免受心肌缺血和再灌注损伤[7]。 Iberiotoxin（三氟乙酸盐）作为 KCa1.1 通道的阻断剂,抑制 db/+ 小鼠海绵体中的乙酰胆碱松弛,而对 db/db 小鼠的组织没有影响[8]。