Nucleic Acids that Encode Sodium Channels

Background:

Mammalian voltage-gated sodium channels are pore-forming membrane proteins responsible for the initiation and propagation of actions in nerve, skeletal muscle, and heart cells. The Na+ channel α-subunit isoforms contain four homologous repeated domains, each with six transmembrane segments (S1-S6). Recent evidence suggests that S6 segments are involved in Na+ channel gating. A number of receptors for various therapeutic drugs and neurotoxins, such as local anesthetics (LAs), antiarrhythmics, anticonvulsants, antidepressants, pyrethroid insecticides, batrachotoxin (BTX), and veratridine, are situated at the middle of multiple S6 segments. Upon binding, these ligands exert their pharmacological actions on the Na+ channel, in part via their corresponding S6 receptor. In particular, BTX drastically modifies Na+ channel activation, fast inactivation, and slow inactivation, suggesting that its receptor is linked to these gating processes.

Technology Overview:

The subject technology is based on the fact that S6 segments may be structurally geared for channel activation by lateral/rotational movement via a flexible gating hinge, a glycine, or serine residue located at the middle of the inner Na+ channel S6 segments. This gating hinge could have two different conformations. One is in its relaxed straight α-helical form, which closes the channel at the S6 C-terminal end. The other is the bendable α-helical form, which may bend outward at a 30° angle and thus splay open the channel at the S6 constricted C-terminus. After channel activation, S6 segments may then form the docking site for the fast-inactivation gate. This could provide a novel method for screening compounds against mutant mammalian voltage-gated Na+ protein for use as anti-arrhythmic agents and other drugs.

Advantages:

This technology provides a novel method for screening compounds for use as anti-arrhythmic agents and other medications, based on mammalian voltage-gated sodium channels.

Applications:

The primary application for this technology is the testing and development of medicinal drugs such as anti-arrhythmic agents.

Intellectual Property Summary:

Issued patent: US8198425B2, “Nucleic acids that encode sodium channel,” https://patents.google.com/patent/US8198425

Stage of Development

TRL 3 - Experimental proof of concept

Licensing Status:

This technology is available for licensing

Licensing Potential

This technology would be of interest to anyone involved in research and development of a variety of drugs such as anti-arrhythmic agents, including:
•    Pharmaceutical companies.
•    Hospitals.
•    Medical research institutions.

Additional Information:

https://www.albany.edu/biology/faculty/sho-ya-wang 
https://www.albany.edu/research/targeting-proteins.php