NS-4591

A Potent Activator of KCa3.1 and KCa2 Channels
    Cat #: N-325
  • Lyophilized Powder
  • Bioassay Tested
  • Source Synthetic
    MW: 258.03
    Purity: >98% (HPLC)
    Effective concentration 0.01-5 μM.
    Structure
    • NS-4591
    Chemical name 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one.
    Molecular formula C11H12Cl2N2O.
    Activity NS-4591 is a potent SK4 channel activator; 30 nM doubled KCa3.1 currents in HEK cells1.
    References-Activity
    1. Hougaard, C. et al. (2009) J. Pharmacol. Exp. Ther. 328, 28.
    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 100 mM 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
    • NS-4591
      Alomone Labs NS-4591 activates KCa3.1 currents expressed in HEK 293T cells.
      A. Time course of KCa3.1 current amplitude and its activation by 1 µM NS-4591 (#N-325). Currents were elicited by application of voltage ramp from -120 mV to +60 mV (150 msec), delivered every 10 seconds, holding potential of -80mV. B. Superimposed example traces of current responses before and during perfusion of 1 µM NS-4591 as indicated.
    References - Scientific background
    1. Wei, A.D. et al. (2005) Pharmacol. Rev. 57, 463.
    2. Hougaard, C. et al. (2009) J. Pharmacol. Exp. Ther. 328, 28.
    Scientific background

    Calcium activated potassium (KCa) channels include three types of small-conductance channels, KCa2.1, KCa2.2 and KCa2.3, and the intermediate conductance channel KCa3.1. Both small- and intermediate-conductance KCa channels play important roles in many processes involving Ca2+-dependent signaling in both electrically excitable and non-excitable cells1.

    NS-4591 is a potent synthetic activator of KCa3.1 and KCa2 channels. It has an effective concentration of 0.01-5 μM. NS-4591 does not seem to affect KCa1.1 or NaV channels but does cause a small reduction in CaV currents and a prominent reduction in delayed rectifier KV channel. In whole-cell patch-clamp experiments conducted, NS-4591 doubled IK-mediated currents at a concentration of 45±6 nM while 530±100 nM was required for doubling of SK3-mediated currents. The effect of NS-4591 was also examined in acutely dissociated bladder primary afferent neurons and NS-4591 was shown to inhibit the number of action potentials generated by suprathreshold depolarizing pulses. NS-4591 reduces the amplitude of detrusor twitches in a concentration dependent manner. in vivo experiments in rats and cats have demonstrated that 30 mg/kg inhibits bladder hyper activity induced by capsaicin and acetic acid. NS-4591 might prove to be an important agent for the treatment of bladder hyperactivity.

    Target KCa3.1, KCa2 channels
    Last update: 24/01/2020

    NS-4591 (#N-325) is a highly pure, synthetic, and biologically active compound.

    For research purposes only, not for human use
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