Tonic and Phasic Guanidinium Toxin-Block of Skeletal Muscle Na Channels Expressed in Mammalian Cells

摘要: The blockage of skeletal muscle sodium channels by tetrodotoxin (TTX) and saxitoxin (STX) have been studied in CHO cells permanently expressing rat Nav1.4 channels. Tonic use-dependent were analyzed the framework ion-trapped model. tonic affinity (26.6 nM) maximum (7.7 TTX, as well “on” “off” rate constants measured this preparation, are remarkably good agreement with those for Nav1.2 expressed frog oocytes, indicating that structure toxin receptor very similar expression method does not any influence on pore properties channel. higher STX (tonic 1.8 nM 0.74 respectively) is explained an increase constant (≈0.03 s−1 nM−1), compared to TTX (≈0.003 while same both toxins (≈0.02 s−1). Estimations free-energy differences toxin-channel interaction indicate bound a more external position than TTX. Similarly, comparison free energy binding ion-free, Na+- Ca2+-occupied channel, consistent site selectivity filter Ca2+ Na+. This data may be useful further attempts at sodium-channel modeling.