Combined Changes in Chloride Regulation and Neuronal Excitability Enable Primary Afferent Depolarization to Elicit Spiking without Compromising its Inhibitory Effects
Fig 7
PAD-mediated inhibition of spike propagation in a multi-compartment axon model.
(A) Cartoon depicts our three-compartment axon model. One or more spikes were initiated by current injection applied to the left end of the axon. Voltage was measured at the midpoint of each compartment; color of traces in B and C correspond to compartment colors shown in A. GABA conductance was distributed uniformly throughout the middle (blue) compartment. (B) For EGABA = -35 mV (left column), gGABA blocked the propagation of the evoked spike under all three combinations of ḡGABA and p that were tested, where p represents the proportion of sodium channels susceptible to inactivation. The gGABA step did not elicit its own spiking in any condition. On the other hand, for EGABA = -20 mV (right column), PAD-induced transient spiking was observed for all three conditions yet propagation of the stimulus-evoked spike was blocked in two of the three conditions. Comparing the top and middle panels shows that modest ḡGABA relies on sodium channel inactivation to block spike propagation, whereas stronger ḡGABA could block propagation without any contribution from sodium channel inactivation. (C) During a spike train, sodium channel inactivation accumulates between spikes such that spikes early in the train can propagate whereas later spikes do not. Comparing with combinations of ḡGABA and p required to block propagation of a single spike (see B), these results show that partial blockade during a spike train can be mediated by even comparatively weak PAD.