Review Article

Acid-Sensing Ion Channels as Potential Therapeutic Targets in Neurodegeneration and Neuroinflammation

Table 2

Exogenous modulators.

CompoundEffectSubunit

Toxins from venomsPcTx1↑ the affinity of the proton, desensitizes the channel [198]ASIC1a, 1a-2b
Hi1aStabilizes the close state of the channel, impeding the transition into a conducting state [199]ASIC1a
APTx2↓ ASIC3 and ASIC3 heteromers [200]ASIC3
MitTx↑ increase the sensitivity of ASIC2a to protons and activate ASIC1a, 1b, and 3 [92]ASIC1a, 1b, 2a, and 3
Mambalgins↓ potent, rapid, and reversible inhibitor of ASICs [86].ASIC1a, 1b, 1a-2a, 1a-2b, and 1a-1b
Ugr 9-1↓ ASIC3 current, including sustained component [201]ASIC3
PhcrTx1↓ ASICs in nDRG [202]All subunits
α-Dendrotoxin↓ ASICs in nDRG [203]?

Vegetal compoundsThalassiolin B↓ ASICs in nDRG [204]Currents with desensitization < 400 ms
Sevanol↓ ASIC1a and 3 (including sustained component) [205]ASIC1a and 3
Gastrodin↓ ASICs in nDRG [206]All subunits
Puerarin↓ ASICs in rat hippocampal neurons and homomers [67]ASIC1a
Chlorogenic acid↓ ASICs in nDRG [207]All subunits
Morphine↓ ASICs in nDRG [208]All subunits
Paeoniflorin↓ ASICs in PC12 cell line [38]ASIC1a
Ligustrazine↓ ASICs in nDRG and ASIC heteromers [134]ASIC1a, 1b, 2a, and 3

Cannabinoids↓ ASICs in nDRG [209]All subunits

NSAIDsSalicylic acid, aspirin, diclofenac, fluribuprofen, ibuprofen, peroxicam↓ homomers and heteromers of ASIC1a, 2a, and 3 [210]ASIC1a, 2a, and 3
CHF5074↓ ASICs in CA1 pyramidal neurons [211]ASIC1a

AnestheticsTetracaine↓ homomeric ASICs and ASICs in nDRG [212]ASIC1a, 1b, and 3
Lidocaine↓ ASIC1a and heteromers [213]ASIC1a and heteromers
Propofol↓ ASICs in nDRG [214]All subunits

AminoglycosidesStreptomicyn, neomicyn, gentamicyn↓ ASICs in nDRG [87]All subunits

Monoamines9-Aminoacridine (9AA)↓ ASICs in rat hippocampal neurons and homomers [215]ASIC1a and ASIC3
Memantine↓ ASICs in hippocampal neurons and homomers [215]ASIC1a, 2a, and 3
IEM1921↑ ASICs in rat hippocampal neurons, ↓ ASIC3 current and potentiated the steady state [215]ASIC1a, ASIC3
IEM2117↑ ASICs in hippocampal neurons and homomers [215]ASIC1a, 2a

OthersAmiloride↓ unspecific inhibitor of ASIC subunits [13]All subunits
4-ChlorophenylguanidineActivating the channel and increasing proton sensitivity [216]ASIC3
GMQ↑ ASIC3 homomers at neutral pH [82]ASIC3
Tetraethylammonium (TEA)↓ heteromeric ASIC currents [23]ASIC1a-2b
4-Aminopyridine (4AP)↓ heteromeric ASIC currents [217]ASIC1a-2a and 1a-2b
A-317567↓ ASICs in nDRG [93]All subunits
Nafamostat mesilate↓ ASIC currents [218]ASIC1a, 2a, and 3
Diarylamidines↓ ASICs in hippocampal neurons and heteromers [219]ASIC1a, 1b, 2a, and 3
Chloroquine↓ ASICs in retinal ganglion neurons and CHO cells [220]ASIC1a
NS383↓ homomeric and heteromeric channels [221]ASIC1a, 3, and heteromers
Omeprazole↑ the expression of ASIC1a in Caco-2 cells [222]ASIC1a
Corticosterone↑ ASIC1a current in hippocampal neurons [223]ASIC1a
InsulinRegulator of ASIC1a membrane surface expression [224]ASIC1a, 2a, and 3
Sulfhydryl compounds↑ peak current and slow-down channel desensitization [158]ASIC1a, 1b, 2a, and 3

↓: inhibits; ↑: increases; nDGR: neurons of dorsal root ganglia; NSAIDs: nonsteroidal anti-inflammatory drugs.