Figure 4
Voltage threshold for action potential generation is unchanged by 4β-phorbol 12-myristate 13-acetate or IFN-β in ex vivo whole-cell recordings of layer 5 neocortical neurons and in silico . (A) Voltage traces showing the first action potential with (green trace) and without (black trace) protein kinase C (PKC) activation (top). Note that due to the rheobase shift (Figure 2A) the first action potential appeared at a current injection of 150 pA under control conditions (black trace) but at 100 pA following 4β-phorbol 12-myristate 13-acetate (4β-PMA) (1 μM) application (green trace). Analysis of voltage thresholds are from the above recordings (according to [32]). The membrane potential at the time of the first peak of the third derivate of the action potential is taken as voltage threshold (bottom). Dots represent time points for estimating voltage thresholds throughout the figure. (B) Population data demonstrate similar voltage thresholds before and during PKC activation with 4β-PMA. (C) Comparable voltage thresholds for action potential generation in voltage trajectories before (black trace) and after 30 minutes of treatment with 1,000 IU ml-1 IFN-β (green trace, left). Again, rheobase shift caused the first action potential to appear already at 220 pA under IFN-β instead of at 350 pA as under control conditions. Population data confirm similar voltage thresholds (right). (D) In silico hyperpolarizing V1/2 of I Nap (adopted from [24]) in our NEURON model by 4 mV does not alter the voltage threshold for action potential generation. ctrl, Control.