Reactome | ASIC trimers:H+ transport extracellular Na+ to cytosol

ASIC trimers:H+ transport extracellular Na+ to cytosol

Stable Identifier

R-HSA-2671885

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, extracellular region, plasma membrane

ReviewStatus

5/5

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ASIC trimers:H+ transport extracellular Na+ to cytosol

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Acid-sensing ion channels 1, 2, 3 and 5 (ASIC1, 2, 3 and 5, aka amiloride-sensitive cation channels) are homotrimeric, multi-pass membrane proteins which can transport sodium (Na+) when activated by extracellular protons. Members of the ASIC family are sensitive to amiloride and function in neurotransmission. The encoded proteins function in learning, pain transduction, touch sensation, and development of memory and fear. Many neuronal diseases cause acidosis, accompanied by pain and neuronal damage; ASICs can mediate the pathophysiological effects seen in acidiosis (Wang & Xu 2011, Qadri et al. 2012). The diuretic drug amiloride inhibits these channels, resulting in analgesic effects. NSAIDs (Nonsteroidal anti-inflammatory drugs) can also inhibit ASICs to produce analgesia (Voilley et al. 2001). ASICs are also partially permeable to Ca2+, Li+ and K+ (not shown here). ASIC1 and 2 are expressed mostly in brain (Garcia-Anoveros et al. 1997, Price et al. 1996), ASIC3 is strongly expressed in testis (de Weille et al. 1998, Ishibashi & Marumo 1998) and ASIC5 is found mainly in intestine (Schaefer et al. 2000). ASIC4 subunits do not form functional channels and it's activity is unknown. It could play a part in regulating other ASIC activity (Donier et al. 2008).

Literature References

PubMed ID	Title	Journal	Year
10767424	Molecular cloning, functional expression and chromosomal localization of an amiloride-sensitive Na(+) channel from human small intestine Schaefer, L, Sakai, H, Mattei, M, Lazdunski, M, Lingueglia, E	FEBS Lett.	2000
9571199	Molecular cloning of a DEG/ENaC sodium channel cDNA from human testis Ishibashi, K, Marumo, F	Biochem. Biophys. Res. Commun.	1998
9744806	Identification, functional expression and chromosomal localisation of a sustained human proton-gated cation channel de Weille, JR, Bassilana, F, Lazdunski, M, Waldmann, R	FEBS Lett.	1998
11588175	Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors Voilley, N, de Weille, J, Mamet, J, Lazdunski, M	J. Neurosci.	2001
8626462	Cloning and expression of a novel human brain Na+ channel Price, MP, Snyder, PM, Welsh, MJ	J. Biol. Chem.	1996
18662336	Regulation of ASIC activity by ASIC4--new insights into ASIC channel function revealed by a yeast two-hybrid assay Donier, E, Rugiero, F, Jacob, C, Wood, JN	Eur. J. Neurosci.	2008
9037075	BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels García-Añoveros, J, Derfler, B, Neville-Golden, J, Hyman, BT, Corey, DP	Proc. Natl. Acad. Sci. U.S.A.	1997