Spider Venom Peptide Pn3a Inhibition of Primary Afferent High Voltage-Activated Calcium Channels.

Despite potently inhibiting the nociceptive voltage-gated sodium (Na) channel, Na1.7, -theraphotoxin Pn3a is antinociceptive only upon co-administration with sub-therapeutic opioid agonists, or by itself at doses >3,000-fold greater than its Na1.7 by a yet undefined mechanism.

Pharmacological characterisation of the highly Na1.7 selective spider venom peptide Pn3a.

Human genetic studies have implicated the voltage-gated sodium channel Na1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits Na1.

Conotoxins That Could Provide Analgesia through Voltage Gated Sodium Channel Inhibition.

Chronic pain creates a large socio-economic burden around the world. It is physically and mentally debilitating, and many suffers are unresponsive to current therapeutics. Many drugs that provide pain relief have adverse side effects and addiction liabilities.

The E1015K variant in the synprint region of the CaV2.1 channel alters channel function and is associated with different migraine phenotypes.

Mutations in the CACNA1A gene, which encodes the pore-forming α1A subunit of the CaV2.1 voltage-gated calcium channel, cause a number of human neurologic diseases including familial hemiplegic migraine. We have analyzed the functional impact of the E1015K amino acid substitution located in the "synprint" domain of the α1A subunit.