NS 1619 is a selective large conductance Ca2+-activated K+-channel activator[1]. The Ca²⁺-activated K⁺ channel is a voltage- and Ca²⁺-gated potassium channel that plays a crucial role in regulating cellular excitability and ion homeostasis[2]. NS 1619 is usually used in research on cardiovascular diseases and cancer[3].
In vitro, treatment of A2780 ovarian cancer cells with NS 1619 (5-100μM; 48h) inhibits cell proliferation in a dosage and time-dependent manner, induces cell apoptosis and DNA fragmentation, increases sub-G1 population, augments whole-cell K+ currents, and increases expression of p53, p21, and Bax proteins[4]. Treatment of rat ventricular myocytes with NS 1619 (10μM; 2min) inhibits L-type Ca²⁺ channels in a dose-dependent manner, and shifts the activation curve to more positive potentials but does not significantly affect the inactivation curve[5].
In vivo, NS 1619 (1mg/kg; i.p.) significantly reduced leukocyte rolling and adhesion, prevented increases in intestinal TNFα levels, and preserved mucosal barrier function in wild-type C57BL/6J mice with intestinal ischemia/reperfusion injury[6]. NS 1619 (1mg/kg; i.p.; 24 hours before ischemia/reperfusion) significantly reduced infarct size and improved postischemic ventricular function in adult male ICR mice[7].
References:
[1] Edwards G, Niederste-Hollenberg A, Schneider J, Noack T, Weston AH. Ion channel modulation by NS 1619, the putative BKCa channel opener, in vascular smooth muscle. Br J Pharmacol. 1994;113(4):1538-1547.
[2] Latorre R, Brauchi S. Large conductance Ca2+-activated K+ (BK) channel: activation by Ca2+ and voltage. Biol Res. 2006;39(3):385-401.
[3] Huang Y, Lau CW, Ho IH. NS 1619 activates Ca2+-activated K+ currents in rat vas deferens. Eur J Pharmacol. 1997;325(1):21-27.
[4] Han X, Xi L, Wang H, et al. The potassium ion channel opener NS1619 inhibits proliferation and induces apoptosis in A2780 ovarian cancer cells. Biochem Biophys Res Commun. 2008;375(2):205-209.
[5] Park WS, Kang SH, Son YK, et al. The mitochondrial Ca2+-activated K+ channel activator, NS 1619 inhibits L-type Ca2+ channels in rat ventricular myocytes. Biochem Biophys Res Commun. 2007;362(1):31-36.
[6] Dai H, Wang M, Patel PN, et al. Preconditioning with the BKCa channel activator NS-1619 prevents ischemia-reperfusion-induced inflammation and mucosal barrier dysfunction: roles for ROS and heme oxygenase-1. Am J Physiol Heart Circ Physiol. 2017;313(5):H988-H999.
[7] Wang X, Yin C, Xi L, Kukreja RC. Opening of Ca2+-activated K+ channels triggers early and delayed preconditioning against I/R injury independent of NOS in mice. Am J Physiol Heart Circ Physiol. 2004;287(5):H2070-H2077.
NS 1619是一种选择性的大电导钙激活钾通道激活剂[1]。钙激活钾通道是一种电压和钙离子门控的钾通道，在调节细胞兴奋性和离子稳态中发挥关键作用[2]。NS 1619常用于心血管疾病和癌症的研究[3]。
在体外，NS 1619 (5-100μM； 48小时) 处理A2780卵巢癌细胞以剂量和时间依赖的方式抑制细胞增殖，诱导细胞凋亡、DNA 片段化，增加sub-G1期细胞比例，增强全细胞K⁺电流，并提高 p53、p21和Bax蛋白的表达[4]。NS 1619（10μM；2分钟）处理大鼠心室肌细胞可剂量依赖性地抑制L型Ca²⁺通道，使激活曲线向更正的电位方向移动，但对失活曲线无显著影响[5]。
在体内，NS 1619（1mg/kg；腹腔注射）可在野生型C57BL/6J小鼠的肠道缺血/再灌注损伤模型中显著减少白细胞滚动和黏附，抑制肠道 TNFα水平升高，并维持黏膜屏障功能[6]。NS 1619（1mg/kg；腹腔注射；缺血/再灌注前24小时给药）可显著减少成年雄性ICR小鼠的心肌梗死面积并改善缺血后的心室功能[7]。