Table 2.
Exogenous modulators.
| Compound | Effect | Subunit | |
|---|---|---|---|
| Toxins from venoms | PcTx1 | ↑ the affinity of the proton, desensitizes the channel [198] | ASIC1a, 1a-2b |
| Hi1a | Stabilizes 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 compounds | Thalassiolin 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 | |
|
| |||
| NSAIDs | Salicylic 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 | |
|
| |||
| Anesthetics | Tetracaine | ↓ 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 | |
|
| |||
| Aminoglycosides | Streptomicyn, neomicyn, gentamicyn | ↓ ASICs in nDRG [87] | All subunits |
|
| |||
| Monoamines | 9-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 | |
|
| |||
| Others | Amiloride | ↓ unspecific inhibitor of ASIC subunits [13] | All subunits |
| 4-Chlorophenylguanidine | Activating 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 | |
| Insulin | Regulator 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.