Structural Characterization of Voltage-Gated Sodium Channels

Voltage-gated sodium (Na_V) channels play an important role in electrical signaling. Creative Bioarray is committed to providing clients with biophysical characterization of Na_V channels to resolve Na_V channel structures to near atomic resolution, which opens a new chapter in the study of Na_V channel structure-function relationships with significant physiological and pathophysiological significance.

Background

In excitable cells, Na_V channels are responsible for generating and propagating action potentials and mediating key physiological processes including nerve signaling, muscle contraction, and hormone release. There are nine subtypes of sodium channels (Na_V1.1-1.9) with highly conserved sequences in humans and these members are specifically expressed in different tissues. Dysfunction of these channels can lead to a variety of life-threatening diseases, such as epilepsy, paroxysmal paralysis, arrhythmia, and allodynia.

Scientists have been working on the structural biology of voltage-gated ion channels for nearly ten years and have achieved a series of important results. Breakthroughs in cryo-electron microscopy have enabled high-resolution visualization of human Na_V1.1, Na_V1.2, Na_V1.4, Na_V1.5, and Na_V1.7 channel subtypes. These structural analyses not only help to reveal the molecular mechanisms of the structure and function of Na_V channels, including ion selectivity, activation, fast inactivation, voltage-sensing, electromechanical coupling, and ligand modulation, also provide atomic-scale templates for the rational development of potential subtype-selective therapeutics.

Fig. 1 The primary structures of the subunits of the voltage-gated sodium channels. (Catterall, 2014)

Our Services

Over the past few years, our research team has worked hard to develop advanced structural characterization techniques such as cryo-electron microscopy to provide detailed elucidation of the structure of Na_V channels from nerves, cardiomyocytes, and skeletal muscle, which is helpful to deepen the basic understanding of the structure and function of Na_V channels. Furthermore, we are able to help clients analyze the high-resolution structure of mammalian Na_V channels in different functional states including the resting state to reveal more detailed information, such as ion selectivity. Our services include but not limited to:

• Cryo-EM structural analysis of Na_V channels. We provide one-stop structural analysis services, including purification of Na_V channel complexes, preparation of high-quality cryo-EM samples, and high-resolution 3D structure elucidation by cryo-EM technology.
• Analysis of assembly of Na_V channel α- and β-subunits.
• Structural analysis of the binding sites of different small molecule modulators to Na_V channel proteins.
• Structural analysis of complexes of Na_V channels and their blockers and gating regulators.
• Analysis of ion path of Na_V channels.

Applications

The Na_V channel structure characterization service we provide, combined with the research on physiological function, ligand regulation and pharmacology, can greatly enrich the knowledge of Na_V channels and accelerate the research on many aspects of Na_V channels.

• Study on the structural basis for sodium selectivity, voltage-dependent activation, and conductance
• Molecular mechanism of Na_V channel disease
• Structural pharmacological study of Na_V channels
• Study on the mechanism of block of the channel by therapeutically important drugs

Creative Bioarray has accumulated extensive experience in the structural characterization of ion channels over the years. We have the strength to provide our clients with structural characterization services of Na_V channels in different tissues and in different states, which helps to accelerate structure-based drug design and develop more effective and safer drugs to treat Na_V channel-related diseases. If you are interested in our services, please contact us for more details.

Reference

1. Catterall, W. A. Structure and function of voltage-gated sodium channels at atomic resolution. Experimental physiology, 2014, 99(1): 35-51.