Mambalgin-1 – Ion Channels and Transporters

Mambalgin-1 was initially isolated by Sylvie Diochot and collaborators from the venom of the black mamba (Dendroaspis polylepis polylepis). Mambalgin-1 is a potent and selective blocker of acid-sensing ion channels (ASIC). ASIC channels have been demonstrated to be implied in pain pathways and appear to be promising therapeutic targets. Mambalgin-1 rapidly and reversibly inhibits recombinant homomeric ASIC1a (IC50=55 nM) and heteromeric ASIC1a+ASIC2a (IC50=246 nM) or ASIC1a+ASIC2b channels (IC50=61 nM) but also human channels hASIC1b (IC50=192 nM) and hASIC1a+hASIC1b (IC50=72nM).Mambalgin-1 belongs to the family of three-finger toxins and has no sequence/structural homology with either PcTx1 or APETx2. Mambalgin-1 differs from mambalgin-2 by one amino acid. Both have demonstrated a similar activity. Mambalgin-1 has no effect on ASIC2a, ASIC3, ASIC1a+ASIC3 and ASIC1b+ASIC3 channels, as well as on TRPV1, P2X2, 5-HT3A, Nav1.8, Cav3.2 and Kv1.2 channels.

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