Recombinant Anthopleura elegantissima Toxin APETx2

This toxin potently blocks acid-sensing ion channel ASIC3 homotrimers and heterotrimers containing ASIC3 (composed with isoforms of ASIC1 and ASIC2). It also weakly inhibits potassium channels, and sodium channels. On homomeric ASIC3, this protein shows IC(50)=57-87 nM on rat, 37.3 nM on mouse and 175 nM on human channels. The blockade is rapid and reversible. On heterotrimeric forms, the toxin is less potent (IC(50)=117 nM on rat ASIC2b-ASIC3 channel, 900 nM on rat ASIC1b-ASIC3, and 2 uM on rat ASIC1a-ASIC3). It weakly inhibits Kv3.4/KCNC4 potassium channels (3 uM of the toxin inhibits 38% of Kv3.4 current). It reversibly and voltage-dependently inhibits hKv11.1/KCNH2/ERG1 potassium channels (IC(50)=1.21 uM), inhibiting both peak and tail currents without action on channel inactivation. It weakly inhibits rNav1.2/SCN2A (EC(50)=114 nM), rNav1.6/SCN8A current (17% at 1 uM of the toxin) and Nav1.8/SCN10A (IC(50)=6.6 uM on human channels expressed in oocytes, EC(50)=55 nM on rat channels expressed in oocytes, and 2.6 uM on rat channels in DRG neurons). It may act on sodium channels by binding at site 1 or close by, when the pore is in an open configuration. In vivo, central injection does not induce neurotoxin symptoms in mice even after 24 hours. However, it abolishes acid-induced pain in rats.