Pharmacological Inhibition of the Voltage-Gated Sodium Channel Na_V1.7 Alleviates Chronic Visceral Pain in a Rodent Model of Irritable Bowel Syndrome.

ABSTRACT: The human nociceptor-specific voltage-gated sodium channel 1.7 (hNa_V1.7) is critical for sensing various types of somatic pain, but it appears not to play a primary role in acute visceral pain. However, its role in chronic visceral pain remains to be determined. We used assay-guided fractionation to isolate a novel hNa_V1.7 inhibitor, Tsp1a, from tarantula venom. Tsp1a is 28-residue peptide that potently inhibits hNa_V1.7 (IC₅₀ = 10 nM), with greater than 100-fold selectivity over hNa_V1.3-hNa_V1.6, 45-fold selectivity over hNa_V1.1, and 24-fold selectivity over hNa_V1.2. Tsp1a is a gating modifier that inhibits Na_V1.7 by inducing a hyperpolarizing shift in the voltage-dependence of channel inactiv

SUBMITTER: Jiang Y 

PROVIDER: S-EPMC8369682 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature