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. 2018 Jan 10;38(2):423–440. doi: 10.1523/JNEUROSCI.1774-17.2017

Figure 8.

Figure 8.

Reduction in leak ERG current contributes to increased excitability following depolarizing step. A, Example responses to ramp current injections with and without a preceding depolarizing current step. Bottom, Difference in I–V responses obtained by subtracting the step + ramp response from the ramp response alone (for details, see Materials and Methods). Black curve recorded under control (ACSF) conditions, and blue curve in CCh. B, Bath application of the GIRK activator ML297 (0.67 μM) hyperpolarizes L5 pyramidal cells. C, Difference I–V response calculated by subtracting ramp response in ML297 from ramp response recorded in ACSF. Initial holding potential adjusted to −65 mV under both conditions. Current injection protocol shown above I–V plot. D, Summary of estimated conductance evoked by depolarizing current steps in control (black symbols), in CCh (blue) and following ML297 application (green). *Step ACSF/CCh: p = 0.0123, T = 3.69, df = 8; ***ML297: p = 1.45E-05, T = 10.21, df = 8; two-sample t test. E, Plot of reversal potential of difference I–V plots. n.s., p = 0.77, two-sample t test. F, Plot of the reduction in ERG-related tail current by CCh. Responses normalized to maximal tail current response evoked by 4 s duration depolarizing steps from −90 to −10 mV (tail current reduction p = 9.1 × 10−4, T = 5.50, df = 7). We found a similar reduction in raw (not normalized) tail current (120 ± 25 to 76.5 ± 27.0 pA; p = 2.9 × 10−4, T = 6.67, df = 7). G, Modulation of responses to weak test depolarizing pulses by conditioning depolarizing step response. Modulation in ACSF assayed in separate experiments than CCh/CCh+Terf. H, Summary plot of the change in the number of spikes evoked by two test pulses under each condition (poststep − pre-step). *p = 0.0199, T = 3.37, df = 5; paired t test. I, Diagram of potential cascade evoked by the conditioning depolarizing step that leads to a reduction in the component of the leak K+ current mediated by ERG channels. The loss of part of the standing K+ current can account for both the depolarization of pyramidal cells and the transient increase in input resistance.