Polypeptide neurotoxins modify gating and apparent single-channel conductance of veratridine-activated sodium channels in planar lipid bilayers

Summary The effects of scorpion and sea anemone polypeptide toxins on partially purified veratridine (VER)-activated Na channels from rat brain were studied at the single-channel level in planar lipid bilayers. The probability of the VER-activated channel being open (P _o ) increased with depolarization;P _o was 0.5 at –40 to –50 mV. Saxitoxin (STX) blocked VER-activated channels with an apparent dissociation constant of about 1nm at –45 mV. The apparent single-channel conductance was approximately 9 pS, similar to that seen in VER-activated Na channels from skeletal muscle transverse tubules. Addition of sea anemone or scorpion polypeptide toxins to VER-activated Na channels resulted in a 19% increase in apparent single-channel conductance and a hyperpolarizing shift in theP _o vs. V _m relation such that the channels were more likely to be open at potentials <40 mV. These effects of the polypeptide toxins on the single-channel properties of VER-activated Na channels may account for the previously described potentiation of VER action by polypeptide toxins.     

Pretreatment with physostigmine, mecamylamine and atropine reduces the impact of soman on the cortical visual evoked potential of the cat

A pretreatment regimen of physostigmine, mecamylamine and atropine was evaluated for its ability to alleviate the impact of soman on visual system function as measured by changes in the cortical visual evoked potential (VEP) of the cat. Data from unprotected animals showed a threshold (30% depression in the VEP) of 6.4 micrograms/kg, while in pretreated animals, the threshold dose was 32.7 micrograms/kg, yielding a protection ratio of 5:1. Extending the time between pretreatment and exposure reduced the degree of protection. Pretreatment also reduced the degree of VEP depression at suprathreshold doses, indicating a therapeutic effect even in cases of severe exposure.