FIGURE 5. Cooperative activation of voltage-gated sodium channels can account for the dynamics of action potential initiation in cortical neurons.

a, Waveform (top) and phase plot (bottom) of action potentials elicited by fluctuating inputs in a conductance-based model that incorporates cooperative activation of sodium channels and closed-state inactivation. Both the action potential onset potential variability and onset rapidness are comparable to the in vivo recordings in Fig. 2. b, c, Same model, but without inter-channel coupling (b), and with Hodgkin–Huxley-like channel activation (c). d–g, Reducing the effective density of available sodium channels through TTX application reversibly reduces action potential amplitude and onset rapidness in cortical neurons in vitro. Shown are action potential waveforms (d) and phase plots of their initial parts (e). f, Time course of action potential onset rapidness in a cortical neuron before, during and after TTX application. g, Reversible reduction in onset rapidness of action potentials by TTX in six neurons. Error bars indicate s.e.m.