Voltage-dependent tetrodotoxin binding to single batrachotoxin-modified Na channels recorded from intact neuroblastoma cells

To clarify the voltage-dependent actions of tetrodotoxin (TTX) on Na channels in cellular membranes, we examined the TTX block of single batrachotoxin-modified Na channels in neuroblastoma cells. We found these Na channels had a high affinity for TTX which decreased e-fold per 35.5 mV depolarization. The decrease in affinity resulted primarily from a decrease in the blocking rate for TTX; the unblocking rate increased slightly with depolarization. While the voltage-dependence of TTX binding to neuroblastoma Na channels was similar to that reported in purified Na channels incorporated in bilayers, the magnitude and voltage-dependence of the rate constants were quite different.