Interaction of naturally occurring neurotoxins and the pyrethroid insecticide deltamethrin with rainbow trout (Oncorhynchus Mykiss) brain sodium channels

摘要

AbstractA radiosodium flux assay was employed to characterize the pharmacological properties of trout brain voltage‐sensitive sodium channels and to define the response of those channels to the synthetic pyrethroid insecticide deltamethrin The uptake of22Na+into trout brain synaptoneurosomes was measured in the presence of a number of sodium channel‐directed ligands The sodium channel activators aconitine, veratridine, and batrachotoxin stimulated22Na+uptake into trout brain synaptoneurosomes in a dose‐dependent manner Batrachotoxin was the most efficacious and potent activator having a maximal sodium uptake at saturating concentrations (Emax) of 6 2 nmol/mg protein and a concentration producing a half maximal response (K0 5) of 3 5 μM Veratridine and aconitine producedEmaxvalues of 3 3 and 3 8 nmol/mg protein andK0 5values of 16 2 and 11 9 μM, respectively Scorpion (Leiurus quinquestriatus) venom (10 μg per incubation) lowered theK0 5of batrachotoxin, aconitine, and veratridine and increasedEmaxfor aconitine and veratridine Concentrations of tetrodotoxin above 1 μM completely inhibited22Na+uptake The effects of the pyrethroid insecticide deltamethrin on activator‐dependent22Na+flux were measured to determine if the hypersensitivity of fish to pyrethroid intoxication was related to intrinsic properties of the piscine sodium channel Deltamethrin (20 μM) enhanced veratridine‐ but not aconitine‐dependent22Na+flux Deltamethrin also caused a three‐fold shift in the potency of batrachotoxin with no effect onEmaxOur results demonstrate the presence of functional sodium channels in trout brain synaptoneurosomes that share many of the pharmacological properties of mammalian voltage‐sensitive sodium channels However, the sodium uptake assay employed in this study has limitations for assessing pyrethroid potencies in pisci