Block of avian cardiac fast sodium channels by tetrodotoxin is enhanced by repetitive depolarization but not by steady depolarization.
The blockade of Na+ channels by tetrodotoxin (TTX) was studied in the avian heart with the maximum rate of rise (Vmax) of phase 0 of the action potential used as an indicator of Na+ conductance (gNa). Inhibition by TTX of Vmax occurred at lower concentrations (IC50 congruent to 20 nM) than those reported in mammalian hearts (IC50, 1 to 10 microM). The IC50 was not affected by K+-induced membrane depolarization. Inhibition of closed Na+ channels by TTX was demonstrated and the degree of inhibition was increased by repetitive excitation. The time constant for recovery (tau Rec) from inactivation of Vmax was increased by TTX, a result consistent with the ability of the toxin to trap Na+ channels in the inactivated state. Reduction of the external Na+ concentration [( Na+]0 by 50% reduced the IC50 5.3-fold. This shift can largely be accounted for by the non-linear relationship between Vmax and gNa, that is, there need not be an important effect of [Na+]0 on toxin binding to its receptor. The interaction between TTX and its receptor in the avian heart is about as sensitive as that observed in peripheral nerve. However, like its less-sensitive mammalian heart counterpart, the TTX-Na+ channel interaction is frequency-dependent and apparently little influenced by membrane voltage or [Na+]0.
D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D006321:Heart / Q000187:drug effects* / Q000196:embryology / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology*
D007473:Ion Channels; D013779:Tetrodotoxin; D012964:Sodium; D011188:Potassium