title: The active guanidinium group of saxitoxin and neosaxitoxin identified by the effects of pH on their activities on squid axon.
abstract: The relative potencies of saxitoxin at pH 7.25 and 8.25 have been determined on the squid giant axon under voltage-clamp conditions or by Vmax of the propagated action potential. Of the two guanidinium groups in saxitoxin, the 7, 8, 9 group has been identified as the biologically active group. The evidence lies in the demonstration of a quantitative agreement between the relative abundance of the protonated, positively charged form of that group at pH's 7.25 and 8.25 (ratio 1.80) with the relative potencies (ratio 1.79) of the toxin. The 1, 2, 3 group is excluded by the lack of agreement between the relative abundance of the protonated form (ratio 1.00) and the relative potencies at these pH's. The 1, 2, 3 group is further excluded by the observation that neosaxitoxin is equally potent at pH 6.50 and 7.25, in spite of a difference of 6-fold in the abundance of a deprotonated hydroxyl group on N-1 which should have influenced the potency.
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects*; D049832:Decapodiformes; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000187:drug effects; D008387:Marine Toxins / Q000494:pharmacology*; D012530:Saxitoxin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*
chemical_list: D006146:Guanidines; D007473:Ion Channels; D008387:Marine Toxins; D012530:Saxitoxin; C034902:neosaxitoxin; D012964:Sodium