ASIC modulators

Interacting proteins, toxins, and pharmacological agents are not included in this table. Only most directly-linked references are indicated. For more exhaustive indication of references see text.

ClassExampleEffectSite of ActionReferences
Divalent cationsCa2+, Ba2+, Mg2+Acidic shift of pH dependence of activation and SSDNot known for shift of pH dependenceBabini et al., 2002; Immke and McCleskey, 2003; Paukert et al., 2004
Pore blockAcidic residues in the pore entry for pore block of ASIC1a
Zn2+Inhibits ASIC1a, ASIC1b, and ASIC3Inhibitory site on the finger domain of ASIC1aChu et al., 2004
Potentiates ASIC2-containing channelsPotentiating sites in thumb and finger of ASIC2aBaron et al., 2001
PolyaminesSpermineAcidic shift of pH dependence of SSD, leading to a current increaseExtracellularBabini et al., 2002; Duan et al., 2011
AgmatineActivates ASIC3Involvement of palmaLi et al., 2010c
Redox reagents and free radicalsH2O2, dithiothreitol, nitric oxidePeak current increase by reducing agents and nitric oxide, inhibition by oxidizing agentsNitric oxide acts extracellularlyAndrey et al., 2005; Chu et al., 2006; Cadiou et al., 2007; Cho and Askwith, 2007
NeuropeptidesFMRFamide, dynorphinShift the pH dependence of SSD to more acidic valuesExtracellularAskwith et al., 2000; Sherwood and Askwith, 2009
Slow the kinetics of desensitization and may induce a sustained current
These effects are observed with ASIC1 and ASIC3 but not ASIC2a
GPCR activatorsSerotonin, cannabinoid receptor agonistsDepending on the compound, potentiation or InhibitionEffects via GPCR or directly on ASICsQiu et al., 2012; Wang et al., 2013
ProteasesTrypsin, tissue kallikreinAcidic shift the pH dependence of activation and SSD of ASIC1aTrypsin cleaves ASIC1a in the finger domainPoirot et al., 2004; Vukicevic et al., 2006; Su et al., 2011
Protein kinasesPKA, PKCAffecting expression and function of ASICsIntracellular phosphorylation sitesBaron et al., 2002; Leonard et al., 2003; Deval et al., 2004; Gao et al., 2005
OtherArachidonic acidIncreases the peak currents and induces in some ASIC types a sustained currentNot knownAllen and Attwell, 2002; Smith et al., 2007
Lactic acidIncreases ASIC currents, most likely by chelating extracellular divalent cationsProbably not acting directly on ASICsImmke and McCleskey, 2001
ATPIncreases pH sensitivity of ASIC3Probably through P2X receptorsBirdsong et al., 2010
  • GPCR, G protein–coupled receptor; PKC, protein kinase C.

  • ↵a One study concluded that the related GMQ binds to the palm of ASIC3, whereas another study showed that mutation of a putative binding site residue affected only one aspect of GMQ function (section VI.A.1.b).