- References (25)
Product nameXE-991 dihydrochloride, KCNQ channel blocker; blocks M current
DescriptionPotent, selective KCNQ channel blocker; blocks M current
Biological descriptionPotent and selective blocker of KCNQ voltage-gated potassium channels. Blocks M current. (IC50 values are 0.98 μM (M-current), 0.71 μM (KCNQ 2), 0.75 μM (KCNQX 1), >100 μM (Kv1.2) and >43 μM (Kv4.3). Potent pulmonary vasoconstrictor. Cognitive enhancer following oral administration in vivo.
Storage instructionsStore at +4°C. Store under desiccating conditions. The product can be stored for up to 12 months.
Soluble in water to 100 mM
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20°C. Generally, these will be useable for up to one month. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.
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To assess the effects of blockade of muscarine-dependent K+ current, IM, under voltage clamp conditions, and to determine if carbachol, CCh, acts through the blockade of an additional conductance other than IM, voltage ramps were performed in ACSF containing TTX (0.5 µM), ZD7288 (50 µM), prior to and during sequential addition of XE-991 (10 µM) and CCh (50 µM) (n=9). Application of XE-991 in the presence of TTX and ZD7288 resulted in a significant increase in current required to hold neurons at −60 mV (−18.1±6.6 pA; N–K: p<0.05).
Bath application of XE-991 (10 µM; white bar) resulted in an inward current in cells held at −60 mV indicating that the cells express IM, and the subsequent perfusion with CCh (50 µM) resulted in an additional inward current, suggesting that CCh blocks a second K+ conductance (*: p<0.05).
Left - Theta burst stimulation (TBP) does not induce long-term potentiation (LTP) under control conditions. Coincident TBP of subthreshold excitatory post-synaptic potentials (EPSPs) and somatic action potentials induced no change in EPSC amplitude in the test (black circles) or control (white circles) pathways. The arrow indicates the timing of the TBP protocol. Example voltage traces show the initial burst of 5 coincident EPSPs and action potentials and a single test burst of 5 subthreshold EPSPs. Example current traces from a single experiment illustrating the mean EPSC response during the baseline (1) and at 30–35 minutes (2) in the test and control pathways.
Right - TBP does induce LTP in the presence of the Kv7 channel inhibitor XE-991 (ab120089). In the presence of XE-991 (10 µM), coincident TBP of subthreshold EPSPs and somatic action potentials induced pathway-specific LTP.
This product has been referenced in:
- Yeung SY & Greenwood IA Electrophysiological and functional effects of the KCNQ channel blocker XE991 on murine portal vein smooth muscle cells. Br J Pharmacol 146:585-95 (2005). Read more (PubMed: 16056238) »
- Robbins J KCNQ potassium channels: physiology, pathophysiology, and pharmacology. Pharmacol Ther 90:1-19 (2001). Read more (PubMed: 11448722) »
- Wang HS et al. Molecular basis for differential sensitivity of KCNQ and I(Ks) channels to the cognitive enhancer XE991. Mol Pharmacol 57:1218-23 (2000). Read more (PubMed: 10825393) »
- Wang HS et al. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science 282:1890-3 (1998). Read more (PubMed: 9836639) »