Class | Example | Effect | Site of Action | References |
---|---|---|---|---|
Divalent cations | Ca2+, Ba2+, Mg2+ | Acidic shift of pH dependence of activation and SSD | Not known for shift of pH dependence | Babini et al., 2002; Immke and McCleskey, 2003; Paukert et al., 2004 |
Pore block | Acidic residues in the pore entry for pore block of ASIC1a | |||
Zn2+ | Inhibits ASIC1a, ASIC1b, and ASIC3 | Inhibitory site on the finger domain of ASIC1a | Chu et al., 2004 | |
Potentiates ASIC2-containing channels | Potentiating sites in thumb and finger of ASIC2a | Baron et al., 2001 | ||
Polyamines | Spermine | Acidic shift of pH dependence of SSD, leading to a current increase | Extracellular | Babini et al., 2002; Duan et al., 2011 |
Agmatine | Activates ASIC3 | Involvement of palma | Li et al., 2010c | |
Redox reagents and free radicals | H2O2, dithiothreitol, nitric oxide | Peak current increase by reducing agents and nitric oxide, inhibition by oxidizing agents | Nitric oxide acts extracellularly | Andrey et al., 2005; Chu et al., 2006; Cadiou et al., 2007; Cho and Askwith, 2007 |
Neuropeptides | FMRFamide, dynorphin | Shift the pH dependence of SSD to more acidic values | Extracellular | Askwith 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 activators | Serotonin, cannabinoid receptor agonists | Depending on the compound, potentiation or Inhibition | Effects via GPCR or directly on ASICs | Qiu et al., 2012; Wang et al., 2013 |
Proteases | Trypsin, tissue kallikrein | Acidic shift the pH dependence of activation and SSD of ASIC1a | Trypsin cleaves ASIC1a in the finger domain | Poirot et al., 2004; Vukicevic et al., 2006; Su et al., 2011 |
Protein kinases | PKA, PKC | Affecting expression and function of ASICs | Intracellular phosphorylation sites | Baron et al., 2002; Leonard et al., 2003; Deval et al., 2004; Gao et al., 2005 |
Other | Arachidonic acid | Increases the peak currents and induces in some ASIC types a sustained current | Not known | Allen and Attwell, 2002; Smith et al., 2007 |
Lactic acid | Increases ASIC currents, most likely by chelating extracellular divalent cations | Probably not acting directly on ASICs | Immke and McCleskey, 2001 | |
ATP | Increases pH sensitivity of ASIC3 | Probably through P2X receptors | Birdsong 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).