ASIC3 Membrane Protein Introduction

Introduction of ASIC3

ASIC3, also known as amiloride-sensitive cation channel 3 (ACCN3) or testis sodium channel 1 (TNaC1), is encoded by ASIC3 gene. It belongs to the ASIC/ENaC superfamily and is predominantly expressed in dorsal root ganglia neurons, especially in nociceptive sensory neurons. Recent studies show that ASIC3 plays an important role in pain perception, especially in high-intensity pain stimulation and acid-induced hyperalgesia. Meanwhile, ASIC3 has been regarded as a potential therapeutic strategy for arthritis.

Basic Information of ASIC3
Protein Name	Acid-sensing ion channel 3
Gene Name	ASIC3
Aliases	ACCN3, SLNAC1, TNAC1
Organism	Homo sapiens (Human)
UniProt ID	Q9UHC3
Transmembrane Times	2
Length (aa)	531
Sequence	MKPTSGPEEARRPASDIRVFASNCSMHGLGHVFGPGSLSLRRGMWAAAVVLSVATFLYQVAERVRYYREFHHQTALDERESHRLIFPAVTLCNINPLRRSRLTPNDLHWAGSALLGLDPAEHAAFLRALGRPPAPPGFMPSPTFDMAQLYARAGHSLDDMLLDCRFRGQPCGPENFTTIFTRMGKCYTFNSGADGAELLTTTRGGMGNGLDIMLDVQQEEYLPVWRDNEETPFEVGIRVQIHSQEEPPIIDQLGLGVSPGYQTFVSCQQQQLSFLPPPWGDCSSASLNPNYEPEPSDPLGSPSPSPSPPYTLMGCRLACETRYVARKCGCRMVYMPGDVPVCSPQQYKNCAHPAIDAMLRKDSCACPNPCASTRYAKELSMVRIPSRAAARFLARKLNRSEAYIAENVLALDIFFEALNYETVEQKKAYEMSELLGDIGGQMGLFIGASLLTILEILDYLCEVFRDKVLGYFWNRQHSQRHSSTNLLQEGLGSHRTQVPHLSLGPRPPTPPCAVTKTLSASHRTCYLVTQL

Function of ASIC3 Membrane Protein

Acid-sensing ion channel 3 (ASIC3) has two hydrophobic transmembrane domains (TM1 and TM2), short intracellular N-and C- termini, and a large cysteine-rich extracellular loop. ASIC3 is extracellular proton-gated cation channel that has been implicated in multiple physiological and pathological processes. ASIC3 has also been shown to play an inhibitory role in synovial proliferation and subsequent accumulation of inflammatory mediators, indicative of a protective effect in joints. Researches reveal that acid sensing ion channel 3 (ASIC3) is the most sensitive to extracellular pH and has the characteristic ability to generate a biphasic current. Acid-sensing ion channel acid-sensing ion channel 3 (ASIC3) has been proposed to be involved in the pathophysiology of hypertension.

Fig.1 Model of the interaction of NHERF-1 with ASIC3. (Deval, 2006)

Application of ASIC3 Membrane Protein in Literature

Yan X.G., et al. Subtype-selective inhibition of acid-sensing ion channel 3 by a natural flavonoid. CNS Neurosci Ther. 2018. PubMed ID: 29781252

This article analyzes the effect of several compounds on the ASIC-mediated currents and acid-induced nocifensive behavior. These results show that small molecule drug can be designed to target ASIC3 channels to treat pain-related diseases.
Zheng M.X., et al. Expression of Nerve Growth Factor and Type 3 of Acid Sensitive Ion Channels in Rat Model of Type Ⅲ Prostatitis. Sichuan Da Xue Xue Bao Yi Xue Ban. 2018, 49(1): 39-43. PubMed ID: 29737087

Authors assess the expression levels of nerve growth factor (NGF) and acid-sensing ion channel 3 (ASIC3) in prostatic tissue of experimental rats with type Ⅲ prostatitis. The data illustrate that NGF and ASIC3 are highly expressed in the prostate with EAP.
Cao Q., et al. Inhibition of Acid Sensing Ion Channel 3 Aggravates Seizures by Regulating NMDAR Function. Neurochem Res. 2018. PubMed ID: 29736613

Authors in this group reveal that ASIC3 expression is increased in the hippocampus of pilocarpine induced seizure rats, as well as in hippocampal neuronal cultures undergoing epileptiform discharge elicited by Mg²⁺-free media and find ASIC3 agonists could be used to seizure treatment.
Er L.K., et al. Combined effect of acid-sensing ion channel 3 and transient receptor potential vanilloid 1 gene polymorphisms on blood pressure variations in Taiwanese. Ci Ji Yi Xue Za Zhi. 2018, 30(1): 29-36. PubMed ID: 29643714

Authors analyze the genetic polymorphisms of the ASIC3 and TRPV1 genes and blood pressure (BP) variations in Taiwanese population. These results indicate that the interaction between ASIC3 and TRPV1 is involved in BP regulation.
Stephan G., et al. The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand-gated cationic channel. Nat Commun. 2018, 9(1): 1354. PubMed ID: 29636447

This article reveals the interaction relationship between acid-sensing ion channels (ASIC3) and of ATP-sensitive P2X receptors (P2X3Rs) in sensory neurons. The receptor sub-units are tightly associate with each other to form a protein complex, mediating unidirectional inhibition.

ASIC3 Preparation Options

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Reference

Deval E, et al. (2006). Regulation of sensory neuron-specific acid-sensing ion channel 3 by the adaptor protein Na+/H+ exchanger regulatory factor-1. J Biol Chem. 281(3): 1796-807.

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