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

Table 3

Endogenous modulators.

	Compound	Effect	Subunit
Neuropeptides	Dynorphin A, big dinorphin	↓ decrease proton sensitivity of steady-state inactivation [65]	ASIC1a
	FMRFamide and related mammalian FF amide peptides.	↑ enhance the sustained current and slow down inactivation [225]	ASIC1a, ASIC1b, and ASIC3
Inflamatory mediators	Nerve grow factor (NGF)	↑ ASIC3 expression associated with hyperalgesia [81]	ASIC3
	Bradiquinine	↑ ASIC mRNA levels [81]	ASIC1a, 1b, 2b, and 3
	Serotonin	↑ ASIC3 sustained current [101]
	Interleucine	↑ ASIC mRNA [81]	ASIC1a, 1b, 2b, and 3
	Arachidonic acid	↑ peak current [106]
	Nitric oxide (NO donors)	↑ increase ASIC1a, 1b, and 3 current [55, 107]
Cations	Ca^2+, Mg^2+, Cd^2+, Cu^2+, Gd^3+, Ni^2+, Pb^2+, Ba^2+	↓ decrease the ASIC conductance [160]	All subunits
	Zn^2+	↓↑ dual effect: at low concentration ↓ the current and high concentration ↑ the current [226]	ASIC1a, 1a-2a, and ASIC2a
	NH4^+	↑ activate ASIC current at extracellular pH 7.4 [35]	ASIC1a
Polyamines	Spermine	↑ activity of ASICs by shifting the steady-state inactivation to more acid values [66]	ASIC1a and 1b
	Agmantine and arcaine	↑ activate ASIC3 current [82, 83]	ASIC3
Others	Lactate	↑ ASIC current [63]	ASIC1a and 3
	ATP	↑ pH sensitivity of ASIC3 [105]	ASIC3
	Cl^−	↑ slow down the rapid desensitization of ASIC1a and maintains tachyphylaxis [227]	ASIC1a
	H2O2	↓ ASIC1a current [228]	ASIC1a