Characterization of Acid-Sensing Ion Channels

Creative Bioarray is committed to integrating various techniques to help clients analyze the structure, function and pharmacological characteristics of acid-sensing ion channels (ASICs). We are confident to provide our clients with professional and high-quality experimental results to accelerate the elucidation of ASIC functions and pathophysiological roles.

Introduction

ASICs are a group of amiloride-sensitive ligand-gated ion channels belonging to the degenin/epithelial sodium channel (DEG/ENaC) family. Currently, six ASIC subtypes encoded by four genes (Accn1, Accn2, Accn3, and Accn4) have been identified, including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3 and ASIC4. They are mainly expressed in the peripheral nervous system and central nervous system and participate in multiple physiological functions, such as sensing the pH value of body fluids, regulating pain and sour taste, memory and fear conditioning, etc.

With the advancement of crystallographic technology, studies based on the crystal structure of ASICs have also emerged, providing important information for studying the expression regulation and opening structural mechanisms of these channels. A variety of valuable pharmacological tools such as potent and selective ASIC modulators have been used to study ASIC structure, function and biological effects. In addition, advances in pharmacological inhibition of individual ASIC currents have accelerated the study of the functional roles of ASICs in physiological and pathophysiological states.

Fig. 1 ASICs localize in multiple somatosensory nerve terminals responsible for both chemo-sensing and mechano-sensing functions. (Cheng, 2018)

Our Services

We help our clients characterize the structure and function of ASICs through crystallographic analysis, site-directed mutagenesis, electrophysiology and other technologies. Our services include but not limited to:

• Analysis of biophysical characteristics of ASICs, such as H⁺-concentration response curve.
• Expression pattern analysis of different ASIC subtypes by genetic or immunohistochemistry tools.
• Structural characterization of ASICs, including the precise structure of the extracellular domain (ECD), and the structure of the transmembrane domains and the ion pore, providing invaluable pictures for modeling ion permeation, selectivity and H⁺-gating of ASICs.
• Identification of regions that are responsible for differential H⁺ sensitivity of different ASICs using chimeric approaches.
• Pharmacological analysis of ASICs. We help clients clarify the role of ASICs in vitro and in vivo, as well as the pharmacology and therapeutic potential of ASIC inhibitors by analyzing the molecular interaction between ASIC inhibitors (metal ions, peptide toxins and small molecule inhibitors) and ASICs.

Applications

• Study on the structural basis of continuous opening and endogenous molecular regulation mechanism of ASICs
• Research on the contribution of ASICs to immune cell function in neuropathology
• Study on the ASIC function and pathophysiological roles

Creative Bioarray has advanced experimental instruments and a professional research team to ensure high-quality ASIC characterization services for our clients. Our professional scientific services and technical support will contribute to your structure-function analysis of ASICs and the development of novel drugs for the treatment of ASICs-related diseases. If you are interested in our services, please contact us for more details.

Reference

1. Cheng, Y. R.; et al. Acid-sensing ion channels: dual function proteins for chemo-sensing and mechano-sensing. Journal of biomedical science, 2018, 25(1): 1-14.