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Last update 08 May 2025

ASIC3

Last update 08 May 2025

Basic Info

Synonyms

ACCN3, acid sensing ion channel subunit 3, acid-sensing (proton-gated) ion channel 3

+ [11]

Introduction

Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Generates a biphasic current with a fast inactivating and a slow sustained phase. In sensory neurons is proposed to mediate the pain induced by acidosis that occurs in ischemic, damaged or inflamed tissue. May be involved in hyperalgesia. May play a role in mechanoreception. Heteromeric channel assembly seems to modulate channel properties.

Drugs associated with ASIC3

Triol

Target

ASIC1 x ASIC3

Mechanism

ASIC1 antagonists [+1]

Active Org.

Morehouse School of Medicine

Originator Org.-

Active Indication

ischemic brain injury [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

THA-902 XL

Target

ASIC3

Mechanism

ASIC3 inhibitors

Active Org.-

Originator Org.

Theralpha S.A.S.

Active Indication-

Inactive Indication

Pain

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

A-317567

Target

ASIC3

Mechanism

ASIC3 modulators

Active Org.-

Originator Org.

Abbott Laboratories

Active Indication-

Inactive Indication-

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ASIC3

100 Translational Medicine associated with ASIC3

0 Patents (Medical) associated with ASIC3

552

Literatures (Medical) associated with ASIC3

01 Apr 2025·Autonomic Neuroscience

Functional knock out of Acid Sensing Ion Channel 3 prevents the exaggerated exercise pressor reflex in rats exercising on a treadmill

Article

Author: Anselmi, Laura ; Ducrocq, Guillaume P ; Ruiz-Velasco, Victor ; Kuczmarski, Matthew J ; Kaufman, Marc P ; Thomas, Gail D ; Higgins, Shannon P

We have compared the cardiovascular responses to treadmill exercise between wild-type (WT) Wistar Kyoto rats with their ASIC3 knock out (KO) counterparts both before and after their femoral arteries were bilaterally ligated. The rats were instrumented with radiotelemetry devices to measure arterial blood pressure and ran at a treadmill speed of 15-20 m/min. We found no difference in the pressor and cardioaccelerator responses to exercise between the WT and the ASIC3 KO rats when their femoral arteries were freely perfused. In contrast, the WT rats, but not the ASIC3 KO rats, displayed significantly larger peak and integrated pressor responses to treadmill exercise after both femoral arteries were ligated for 3 days. We also examined the effect of bilaterally injecting APETx2 into the substance of the gastrocnemius muscles on the cardiovascular responses to treadmill exercise in both the WT and the ASIC3 KO rats. We found that APETx2, an ASIC3 antagonist, attenuated the integrated pressor responses to exercise in the WT rats, after but not before the femoral arteries were ligated. Injection of APETx2 into the gastrocnemius muscles had no effect on the responses to exercise in the ASIC3 KO rats regardless of whether their femoral arteries were freely perfused or ligated. Our findings in conscious rats exercising on a treadmill extend our previous findings in reduced preparations in which we reported that ASIC3 "receptors" presumably on the intramuscular endings of group IV afferents play an important role in evoking the exaggerated component of the exercise pressor reflex induced by ischemia.

01 Mar 2025·Journal of Biological Chemistry

Spider-derived peptide LCTx-F2 suppresses ASIC channels by occupying the acidic pocket

Article

Author: Zhang, Zhongzhe ; Liu, Changjun ; Liu, Guohao ; Rong, Mingqiang ; Yuan, Fuchu ; Deng, Meichun ; Hou, Wenqian ; He, Ziyan ; Du, Canwei

Acid-sensing ion channels (ASICs) are proton-evoked sodium ion channels, highly distributed in the peripheral and central nervous system. ASICs are involved in pain perception, and ASIC3 channel is presumed as the target of promising analgesics. Peptide drugs have attracted the attention of pharmaceutical developers because of their advantages such as low toxic side effects and targeted specificity. Although numbers of chemicals acting on ASICs are emerging, there are limited reports on peptide inhibitor acting on ASIC3 channel. Here, we found that spider-derived peptide LCTx-F2 suppressed the activity of ASIC3 channel in a concentration-dependent manner. By performing peptide mutation and molecular docking, we revealed the molecular mechanism of LCTx-F2 inhibiting ASIC3 channel, in which β-hairpin of LCTx-F2 penetrated the acidic pocket of the channel. Similarly, LCTx-F2 also inhibited ASIC1a channel by occupying the acidic pocket, but N terminus of the peptide sticked into the region. The bond relationship between critical residues of LCTx-F2 and the channels was uncovered by molecular docking and dynamic simulation. Thus, our findings indicated the molecular mechanism by which LCTx-F2 acts on ASIC3 and ASIC1a channels and provided a novel template of analgesic drug targeting the channels.

31 Jan 2025·Science Advances

A role for proprioceptors in sngception

Article

Author: Lin, Shing-Hong ; Chang, Chu-Ting ; Lee, Cheng-Han ; Hochgeschwender, Ute ; Wu, Yu-Wei ; Gründer, Stefan ; Chen, Chih-Cheng ; Banks, Robert W. ; Bewick, Guy ; Lin, Jiann-Her

Proprioceptors are primary mechanosensory neurons to monitor the status of muscle contraction and/or body position ( 1 ). Although proprioceptors are known as non-nociceptive mechanoreceptors, they also express the pro-nociceptive acid-sensing ion channel 3 (ASIC3) ( 2 – 5 ). To probe the role for proprioceptors in sensing acidosis (or sngception) ( 6 ), we found that genetic deletion of Asic3 in proprioceptors but not in nociceptors abolished acid-induced chronic hyperalgesia in mice. Chemo-optogenetically activating proprioceptors resulted in hyperalgesic priming that favored chronic pain induced by acidosis. In humans, intramuscular acidification induced acid perception but not pain. Conversely, in a spinal cord–injured patient who lost pain sensation in the right leg, proprioception and sngception were remaining somatosensory functions, associated with the spinal dorsal column. Together, evidence from both mouse and human studies suggests a role for proprioceptors in sngception.

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ASIC3

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