ProTx-II is a potent, selective Nav1.7 blocker.

ProTx-II is a potent, selective Nav1.7 blocker. Voltage-gated sodium channels (Nav) are responsible for transducing extracellular signals into action potentials in excitable cells. The Nav1 family consists of nine sub-types for which selective tools are highly valued. Discovery of subtype-selective tools has been challenging due to conservation of putative binding sites. Nav1.7 is expressed in sensory neurons and is critical for pain processing. ProTx-II, isolated from the tarantula Thrixopelma pruriens, is a potent blocker of Nav1 channels. Although ProTx-II blocks several members of this channel family, it has >100-fold selectivity for Nav1.7. ProTx-II is active in an in vitro model of pain processing. ProTx-II binds to a previously unknown site on the channel, conferring selectivity and increasing its value as a research tool. It blocks Nav1.7 by decreasing conductance and shifting the activation potential in the positive direction, resulting in an overall decrease in excitability.