ASIC Channel Modulator II, GMQ

A positively charged guanidium-containing quinazoline that modulates ASIC (acid-sensing ion channel) function by blocking acid-induced maximal peak current (IC₅₀ = 3.24 mM and 1.52 mM, respectively, against pH 4.5-induced human ASIC1a and rat ASIC1b peak current; IC₅₀ = 6.74 mM against pH 5.0-induced rat ASIC3 peak current; by whole-cell patch clamp) as well as by altering ASICs pH dependence for activation (pH₅₀ with/without 1 mM GMQ = 6.30/6.49, 6.14/6.27, and 6.94/6.71, for hASIC1a, rASIC1b, and rASIC3, respectively) and inactivation (pHIn₅₀ with/without 1 mM GMQ = 6.92/7.11, 6.48/6.66, and 6.59/7.07, for hASIC1a, rASIC1b, and rASIC3, respectively; pHIn₅₀ with/without 5 mM GMQ = 5.42/5/63 for rASIC2b) in a dose-dependent manner (EC₅₀ of hASIC1a ΔpH₅₀ = 1.97 mM). The combined pH sensitivity shift, activation reduction, and inactivation blockage enables a partial, but sustained ASIC3 activation around neutral pH by GMQ (4.4% of pH 5-induced peak current by 1 mM GMQ at pH 7.4), which is inhibitable by Amiloride (Cat. No. 129876) in a dose-dependent manner (IC₅₀ against 0.5 mM GMQ activated channel activity at pH 7.0 by Amiloride = 98.5 µM). Likewise, GMQ intraplantar paw injection (10 µL 100 µM) is reported to elicit a pain response in asic3^+/+, but not asic3^-/-, mice (538% vs 14%, respectively, above background paw licking response) in vivo. GMQ targeting area appears to overlap with Amiloride binding site in the pore region, but is distinct from ASIC calcium binding site.

A positively charged guanidium-containing quinazoline that modulates ASIC function by blocking acid-induced maximal peak current as well as by altering ASICs pH dependence for activation and inactivation, enabling a partial, but sustained ASIC3 activation around neutral pH (4.4% of pH 5-induced peak current with 1 mM GMQ at pH 7.4), which is inhibitable by Amiloride (Cat. No. 129876). Intraplantar paw injection (10 µL 100 µM) is reported to elicit a pain response in asic3^+/+, but not asic3^-/-, mice in vivo. GMQ targeting area appears to overlap with Amiloride binding site in the pore region, but is distinct from ASIC calcium binding site.

Primary Target
ASIC3

Reversible: yes

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Alijevic, O., and Kellenberger, S. 2012. J Biol Chem.287, 36059.

Sherwood, T.W., et al. 2012. Am. J. Physiol. Cell Physiol.303, C699.
Yu, Y., et al. 2010. Neuron.68, 61.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany