TABLE 4

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.

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
Divalent cations	Ca²⁺, Ba²⁺, Mg²⁺	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 palm^{^a}	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).