Figure 12. Modelling study of the mAHP following a train of APs.

A, train of APs evoked by a current pulse (50 ms) while holding the membrane potential at −60 mV by steady-state current. Simulations were repeated with and without sAHP current. The left- and right-hand panels show the same simulations at different time scales. B1, same protocol as A while holding the membrane potential at different levels as indicated. Voltage responses of simulations of normal conditions or with either ‘no I_m’ or ‘no I_h’ are shown superimposed. The inset in B1 shows the AHPs following a five-spike train evoked at −60 mV, in normal conditions (control, continuous line), without I_m (‘no I_m’, dashed line) and with a −7 mV negative shift of the I_m steady-state activation curve, i.e. resembling the retigabine effect (thin dotted line). Note that blocking I_m, or shifting its activation curve, increases and decreases the sAHP, respectively. B2 and B3, I_m and I_h response, respectively, during the protocol shown in B1. C, left panel, summary data of the mAHP amplitude at various holding potentials with or without sAHP current. Right panel, voltage dependence of the amplitude of the isolated mAHP (i.e. without sAHP current) with either I_m or I_h blocked. D, to determine whether I_m and I_h are activated and deactivated, respectively, by the APs or by the interspike depolarized plateau during a spike train (as in B), we compared I_m and I_h during voltage responses with and without spikes. The voltage responses from the simulations in B1 at −60 and −80 mV, with or without spikes, were used as voltage-clamp commands (lower panels, dashed traces and continuous lines, respectively). The APs were clipped at the threshold. Upper panels, I_m (left) and I_h (right) during the voltage-clamp command, before (dashed traces) and after (continuous lines) clipping the APs. Note that I_m was strongly reduced by eliminating the spikes, indicating that it was mainly activated during the APs. In contrast, I_h was little affected by clipping the spikes, showing that it was mainly activated by the depolarized plateau. Inset scale bar of B1: 100 ms, 2 mV.