Slow-Current Kinetics and Alkaloid Binding

In agreement with the binding hypothesis it is observed that agents which suppress inactivation of Na+ channels also enhance the veratridine action, obviously by increasing the probability of state O which in turn feeds O. This is true for pronase (Scruggs and Narahashi 1982), 

Other consequences of the binding hypothesis are as follows. During trains of depolarizing pulses the peak Na current (corresponding to 0) should decrease at the rate with which the tail current (0 ) increases. This has been found in frog muscle (Sutro 1986), neuroblastoma cells (Barnes and Hille 1988), and frog nerve in which, however, the reverse process. 

In frog nerve the steady-state current increased with [VT] but not its rate of development (Rando 1989). Likewise, in the more classical approach of suddenly applying alkaloid to the depolarized frog nerve, the time constant (several seconds) of the slowly developing inward current depended only weakly on [VT] (Ulbricht 1972a). These results are presented in more detail below (Sect. 2.4). 

---