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