Iberiotoxin (trifluoroacetate salt)
目录号 : GC43886Selective blocker of KCa1.1/BK channels
Cas No.:182897-30-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >95.00%
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- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Rat MSCs |
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Preparation Method |
Rat MSCs were plated in 24-well plates in DMEM. When the cells reached confluence, a linear wound was made by scratching the cell monolayer with a pipette tip. Cells were incubated with fresh medium for 24 h in the presence of BK channel modulators (Iberiotoxin (trifluoroacetate salt) 10 nM). |
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Reaction Conditions |
Iberiotoxin (trifluoroacetate salt) 10 nM for 24h |
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Applications |
In the absence of PL, Iberiotoxin (trifluoroacetate salt) treatment affected rMSC migration by inducing reduced cell migration. 10 nM of Iberiotoxin (trifluoroacetate salt) abolishes the PL-induced migration effect on MSCs. |
| Animal experiment [2]: | |
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Animal models |
Male Wistar rats (6-7 weeks old) |
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Preparation Method |
Male Wistar rats were randomized to sham operated group and CHF group. Two weeks after operation, Iberiotoxin (trifluoroacetate salt) was infused into PVN by osmotic minipumps |
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Dosage form |
0.125、1.25、12.5 nmol/nl Iberiotoxin (trifluoroacetate salt) for 4 weeks |
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Applications |
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. |
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References: [1]. 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. [2]. 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. |
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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]。< /p>
| Cas No. | 182897-30-9 | SDF | |
| 分子式 | 分子量 | 4230.9 | |
| 溶解度 | Water: Soluble | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.2364 mL | 1.1818 mL | 2.3636 mL |
| 5 mM | 0.0473 mL | 0.2364 mL | 0.4727 mL |
| 10 mM | 0.0236 mL | 0.1182 mL | 0.2364 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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Iberiotoxin-induced block of Ca2+-activated K+ channels induces dihydropyridine sensitivity of ACh release from mammalian motor nerve terminals
J Pharmacol Exp Ther2003 May;305(2):646-52.PMID: 12606686DOI: 10.1124/jpet.102.046102
The role which Ca(2+)-activated K(+) (K(Ca)) channels play in regulating acetylcholine (ACh) release was examined at mouse motor nerve terminals. In particular, the ability of the antagonist iberiotoxin to recruit normally silent L-type Ca(2+) channels to participate in nerve-evoked release was examined using conventional intracellular electrophysiological techniques. Incubation of cut hemidiaphragm preparations with 10 microM nimodipine, a dihydropyridine L-type Ca(2+) channel antagonist, had no significant effect on quantal content of end-plate potentials. Nevertheless, 1 microM S-(-)-1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-[trifluoromethyl]phenyl)-3-pyridine carboxylic acid methyl ester (Bay K 8644) enhanced quantal content to 134.7 +/- 3.5% of control. Iberiotoxin (150 nM) increased quantal content to 177.5 +/- 9.9% of control, whereas iberiotoxin plus nimodipine increased quantal content to only 145.7 +/- 10.4% of control. Coapplication of 1 microM Bay K 8644 with iberiotoxin did not significantly increase quantal content further than did treatment with iberiotoxin alone. The effects of iberiotoxin and nimodipine alone or in combination on the miniature end-plate potential (MEPP) frequency following KCl-induced depolarization were examined using uncut hemidiaphragm preparations. Nimodipine alone had no effect on MEPP frequency from preparations incubated in physiological saline containing 5 to 20 mM KCl. Moreover, iberiotoxin alone or combined with nimodipine also had no effect on MEPP frequency in physiological salines containing 5 to 15 mM KCl. At 20 mM KCl, however, iberiotoxin significantly increased MEPP frequency to 125.6% of iberiotoxin-free values; combined treatment with nimodipine and iberiotoxin prevented this increase in MEPP frequency. Thus, loss of functional K(Ca) channels unmasks normally silent L-type Ca(2+) channels to participate in ACh release from motor nerve terminals, particularly under conditions of intense nerve terminal depolarization.
Iberiotoxin-sensitive and -insensitive BK currents in Purkinje neuron somata
J Neurophysiol2013 May;109(10):2528-41.PMID: 23446695DOI: 10.1152/jn.00127.2012
Purkinje cells have specialized intrinsic ionic conductances that generate high-frequency action potentials. Disruptions of their Ca or Ca-activated K (KCa) currents correlate with altered firing patterns in vitro and impaired motor behavior in vivo. To examine the properties of somatic KCa currents, we recorded voltage-clamped KCa currents in Purkinje cell bodies isolated from postnatal day 17-21 mouse cerebellum. Currents were evoked by endogenous Ca influx with approximately physiological Ca buffering. Purkinje somata expressed voltage-activated, Cd-sensitive KCa currents with iberiotoxin (IBTX)-sensitive (>100 nS) and IBTX-insensitive (>75 nS) components. IBTX-sensitive currents activated and partially inactivated within milliseconds. Rapid, incomplete macroscopic inactivation was also evident during 50- or 100-Hz trains of 1-ms depolarizations. In contrast, IBTX-insensitive currents activated more slowly and did not inactivate. These currents were insensitive to the small- and intermediate-conductance KCa channel blockers apamin, scyllatoxin, UCL1684, bicuculline methiodide, and TRAM-34, but were largely blocked by 1 mM tetraethylammonium. The underlying channels had single-channel conductances of ∼150 pS, suggesting that the currents are carried by IBTX-resistant (β4-containing) large-conductance KCa (BK) channels. IBTX-insensitive currents were nevertheless increased by small-conductance KCa channel agonists EBIO, chlorzoxazone, and CyPPA. During trains of brief depolarizations, IBTX-insensitive currents flowed during interstep intervals, and the accumulation of interstep outward current was enhanced by EBIO. In current clamp, EBIO slowed spiking, especially during depolarizing current injections. The two components of BK current in Purkinje somata likely contribute differently to spike repolarization and firing rate. Moreover, augmentation of BK current may partially underlie the action of EBIO and chlorzoxazone to alleviate disrupted Purkinje cell firing associated with genetic ataxias.
KCa1.1 β4-subunits are not responsible for iberiotoxin-resistance in baroreceptor neurons in adult male rats
Int J Cardiol2015 Jan 15;178:184-7.PMID: 25464250DOI: 10.1016/j.ijcard.2014.10.128
Several studies suggested that potassium channels are involved in the proliferation of cancer cells but the involvement of the large conductance Ca2+-activated K+ channels (BKCa) in the cancerous phenomenon is still controversial. In the present study, we used iberiotoxin, a specific blocker of BKCa, and report the activity of an iberiotoxin-sensitive current in various human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-468 and MDA-MB-435s) as well as in normal mammary epithelial cells (HME). Iberiotoxin and NS1619, an activator of BKCa, did not interfere with either cell proliferation or with the invasive properties of the cells, under normal culture conditions. However, extracellular pulses of ATP, which induced transient increases in intracellular Ca2+ concentration, revealed a significant reduction effect of iberiotoxin on cell proliferation. We conclude that the iberiotoxin-sensitive current is not involved in cell proliferation in basal conditions but participates when the intracellular Ca2+ concentration is increased. These experiments also suggest that BKCa channels are not involved in the cancerous transformation and are probably a relic from normal cells.
Description and role in proliferation of iberiotoxin-sensitive currents in different human mammary epithelial normal and cancerous cells
Biochim Biophys Acta2004 Dec 15;1667(2):190-9.PMID: 15581855DOI: 10.1016/j.bbamem.2004.10.002
Several studies suggested that potassium channels are involved in the proliferation of cancer cells but the involvement of the large conductance Ca2+-activated K+ channels (BKCa) in the cancerous phenomenon is still controversial. In the present study, we used iberiotoxin, a specific blocker of BKCa, and report the activity of an iberiotoxin-sensitive current in various human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-468 and MDA-MB-435s) as well as in normal mammary epithelial cells (HME). Iberiotoxin and NS1619, an activator of BKCa, did not interfere with either cell proliferation or with the invasive properties of the cells, under normal culture conditions. However, extracellular pulses of ATP, which induced transient increases in intracellular Ca2+ concentration, revealed a significant reduction effect of iberiotoxin on cell proliferation. We conclude that the iberiotoxin-sensitive current is not involved in cell proliferation in basal conditions but participates when the intracellular Ca2+ concentration is increased. These experiments also suggest that BKCa channels are not involved in the cancerous transformation and are probably a relic from normal cells.
Mode of action of iberiotoxin, a potent blocker of the large conductance Ca(2+)-activated K+ channel
Biophys J1992 Aug;63(2):583-90.PMID: 1384740DOI: 10.1016/S0006-3495(92)81630-2
Iberiotoxin, a toxin purified from the scorpion Buthus tamulus is a 37 amino acid peptide having 68% homology with charybdotoxin. Charybdotoxin blocks large conductance Ca(2+)-activated K+ channels at nanomolar concentrations from the external side only (Miller, C., E. Moczydlowski, R. Latorre, and M. Phillips. 1985. Nature (Lond.). 313:316-318). Like charybdotoxin, iberiotoxin is only able to block the skeletal muscle membrane Ca(2+)-activated K+ channel incorporated into neutral-planar bilayers when applied to the external side. In the presence of iberiotoxin, channel activity is interrupted by quiescent periods that can last for several minutes. From single-channel records it was possible to determine that iberiotoxin binds to Ca(2+)-activate K+ channel in a bimolecular reaction. When the solution bathing the membrane are 300 mM K+ internal and 300 mM Na+ external the toxin second order association rate constant is 3.3 x 10(6) s-1 M-1 and the first order dissociation rate constant is 3.8 x 10(-3) s-1, yielding an apparent equilibrium dissociation constant of 1.16 nM. This constant is 10-fold lower than that of charybdotoxin, and the values for the rate constants showed above indicate that this is mainly due to the very low dissociation rate constant; mean blocked time approximately 5 min. The fact that tetraethylammonium competitively inhibits the iberiotoxin binding to the channel is a strong suggestion that this toxin binds to the channel external vestibule. Increasing the external K+ concentration makes the association rate constant to decrease with no effect on the dissociation reaction indicating that the surface charges located in the external channel vestibule play an important role in modulating toxin binding.