Functional Characterization of Voltage-Gated Sodium Channels

Malfunction and dysregulation of voltage-gated sodium (Na_V) channels largely contribute to the electrical hyperexcitability characteristic of neuropathic pain and chronic inflammation. Creative Bioarray is committed to developing multiple biological and chemical approaches to help clients characterize the physiological functions of Na_V channels, providing important information for understanding the role of Na_V localization, regulation, and transport in electrogenesis and pain pathogenesis.

Introduction

Ten loci encoding the Na_V α-subunit have been identified, of which nine (Na_V1.1 to 1.9) are voltage-dependent, and the tenth is Na_Vx, which is involved in salt sensing. Different Na_V isomers exhibit different voltage-dependent and gating properties. Subtle variations in channel expression levels and cellular distribution, as well as the intrinsic gating properties of each subtype, result in a diversity of AP signaling output, determining signaling thresholds and dictating electrical responses to generator stimuli.

In human and animal disease models, there is significant evidence that tissue and nerve injury alters the expression and localization of multiple Na_V isoforms, resulting in ectopic AP firing patterns that lead to symptoms such as mechanical allodynia and thermal hyperalgesia. Although the involvement of Na_V in inflammation and neuropathic pain has been extensively studied over the past few decades, the changes in the subcellular distribution of specific Na_V subtypes induced by injury and the role of specific Na_V subtypes in inflammatory and neuropathic pain are still unclear.

Fig. 1 Tissue expression of Na_V subtypes and effects of Na_V dysfunction on physiology. (Manuel, 2015)

Our Services

We are committed to developing a variety of chemical and biological methods that allow selective manipulation of specific Na_V channel types and develop their potential applications in measuring Na_V expression, localization, trafficking and turnover, so as to provide useful information for the study of the physiological function of Na_V channels. Our services include but not limited to:

• Functional characterization of Na_V channels by chemical methods.
  We provide a variety of strategies such as identification of subtype selective Na_V modulators, semi-synthetic modification of natural toxins, and small molecule design to obtain new insights into Na_V physiology. The chemical tools we can provide to study Na_V channels include animal toxins, radiolabeled probes, crosslinking probes, photocaged probes, and fluorescent probes. Through these tools, we help our customers achieve:
• Mapping of Na_V toxin receptor sites.
• Quantification, separation, and imaging of select Na_V channel subtypes in models of injury or inflammation.
• Monitoring changes in Na_V channel trafficking and localization in healthy cells and the response to injury.
• Detection of changes in Na_V concentration at the site of nerve injury.
• Functional characterization of Na_V channels by biological methods.
  Compared with the successful application of small molecules and Na_V-selective reagents, the availability of biotechnology and tools has made greater contributions to the physiological research of Na_V channels, providing higher accuracy for targeting Na_V channels. The biological tools we can provide to study Na_V channels include antibody labeling, oligonucleotide-based knockdown, optogenetics, and fluorescent and epitope tagging. We provide customers with the following services:
• Preparation of animal models of specific Na_V isomer knockout.
• Design of dually tagged sodium channels.
• Live cell monitoring of membrane Na_V channels.
• Measurement of changes in channel trafficking in response to mediators of inflammatory pain.

Creative Bioarray has developed a variety of biological and chemical strategies to provide clients with Na_V functional characterization services. Our unique technologies and professional scientific services will help you clarify the physiological functions of Na_V channels and the regulatory pathways that underlie Na_V physiology in healthy and aberrant cells. If you are interested in our services, please contact us for more details.

Reference

1. Manuel, D. L. R.; Kraus, R. L. Voltage-gated sodium channels: structure, function, pharmacology, and clinical indications. Journal of medicinal chemistry, 2015, 58(18): 7093-7118.