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A Positive Modulator of Small- and Intermediate-Conductance KCa Channels

Cat #: N-180
Lyophilized Powder yes
  • Bioassay Tested
  • Source Synthetic
    MW: 231.04
    Purity: >99% (HPLC)
    Effective concentration 0.1 - 10 µM.
    Chemical name 6,7-Dichloro-1H-indole-2,3-dione 3-oxime.
    Molecular formula C8H4Cl2N2O2.
    CAS No.: 18711-16-5
    Activity NS-309 is a positive modulator of small- and intermediate- conductance Ca2+-activated K+ (KCa2 and KCa3.1) channels, with EC50 values of 30 and 10 nM, respectively1. NS-309 also blocks L-type Ca2+ channels with IC50 value of 10 μM2.
    1. Strøbaek, D. et al. (2004) Biochim Biophys. Acta. 1665, 1.
    2. Morimura, K. et al. (2006) J. Pharmacol. Sci. 100, 237.
    Shipping and storage Shipped at room temperature. Product as supplied can be stored intact at room temperature for several weeks. For longer periods, it should be stored at -20°C.
    Solubility DMSO. Centrifuge all product preparations before use (10000 x g 5 min).
    Storage of solutions Up to four weeks at 4°C or three months at -20°C.
    Our bioassay
    • Alomone Labs NS-309 enhances KCa3.1 channel currents in HEK293T cells.
      Alomone Labs NS-309 enhances KCa3.1 channel currents in HEK293T cells.
      A. Time course of KCa3.1 channel activity at -10 mV demonstrating the dose-dependent effects of 1 nM -10 μM NS-309 (#N-180). B. Representative current traces under control conditions and following application of 1 nM - 10 μM NS-309. Currents were elicited by a 150 ms voltage ramp from -120 to 60 mV every 10 seconds from a holding potential of -80 mV (current responses are shown between -120 and 0 mV).
    References - Scientific background
    1. Kohler, M. et al. (1996) Science 273, 1709.
    2. Stocker, M. et al. (2000) Mol Cell Neurosci. 15, 476.
    3. Ishii, T.M. et al. (1997) Proc. Natl. Acad. Sci. U.S.A 94, 11651.
    4. Jensen, B.S. et al. (1998) Am. J. Physiol. 275, C848.
    5. Strøbaek, D. et al. (2004) Biochim Biophys. Acta. 1665, 1.
    6. Pedarzani, P. et al. (2005) J. Biol. Chem. 280, 41404.
    7. Singh, S. et al. (2001) J. Pharmacol. Exp. Ther. 296, 600.
    8. Morimura, K. et al. (2006) J. Pharmacol. Sci. 100, 237.
    Scientific background

    Ca2+-activated potassium channels (KCa) are a group of 6/7-TM proteins that selectively transport K+ ions across biological membranes. They are broadly classified into three subtypes: SK, IK and BK channels (small, intermediate and big conductance, respectively). Three SK channel subtypes exist (SK1-3, KCa2.1-3)1 and are widely distributed in the central nervous system (CNS)1-2 as well as in the periphery. They constitute a molecular family of voltage-independent channels with the peripherally expressed intermediate conductance Ca2+-activated K+ channel (IK, KCa3.1)3, but differ in their distribution; SK channels are predominantly expressed in excitable cells, whereas IK channels mostly are found in non-excitable cells3-4.

    NS-309 is a selective and potent activator of KCa3.1 and KCa2 channels, whereas it is devoid of effect on BK (KCa1.1) type channels5-6. Whole cell currents, obtained by voltage ramps applied to HEK293 cells, reveal that human KCa2 channels are two to four times less sensitive to NS-309 than human KCa3.1; NS-309 increases the KCa2 currents with an EC50 value of 30 nM, whereas an EC50 value of 10 nM is inferred for the KCa3.1 currents5.

    NS-309 possesses a therapeutic potency for cystic fibrosis and chronic obstructive pulmonary disease by improving epithelial Cl- secretion via KCa3.1 channel activation7 and for moderating neuronal hyperexcitability by enhancing apamin-sensitive after-hyperpolarizing current (IAHP, mediated by KCa2 channels)5-6.

    NS-309 shows substantial block of L-type Ca2+ channel. It concentration-dependently inhibits the ICa in smooth muscle cells isolated from mouse urinary bladder with an IC50 value of 10.6 mM8. However, the specificity of NS-309 for the KCa3.1 channel over VDCC is much higher.

    Target KCa2 and KCa3.1 K+ channels
    Last update: 06/11/2022

    NS-309 (#N-180) is a highly pure, synthetic, and biologically active compound.

    For research purposes only, not for human use
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