Figure 4.
sDBS-mediated modulation of Ih. A, Representative current-clamp recording and V–I relationship (20 pA for each step) obtained during control (i) and sDBS (ii)(n = 5). B, Representative voltage-clamp recording and I–V relationship (10 mV for each step) obtained from another neuron. i, In control, Ih is seen as a slowly activating inward current on the hyperpolarizing steps (n = 6). ii, During extracellular sDBS, the time dependency of Ih activation is nearly absent as the current is activated tonically with the onset of sDBS and consequently has reached steady state before application of the hyperpolarizing test pulse. All data are derived from ZD7288 (20 μm)-sensitive current and obtained after subtracting ZD7288-resistant currents from the controls (n = 6). iii, A comparison of holding current before or during sDBS. Cells were held at –70 mV. Note that sDBS increased the holding current from control levels (p < 0.001), but this sustained inward current was blocked by ZD7288. iv, Ih activation curve obtained based on the ratio of Ii versus Imax (control step to –120 mV). v, I–V relationship for instantaneous (Ii) and steady-state (Imax) current. Imax was obtained at the end of each 1 s voltage step. During sDBS, a significant increase in instantaneous and steady-state current was observed over control (p < 0.001). However, there was no statistical difference between instantaneous and steady-state current that developed during sDBS. This indicates a tonic activation of Ih induced by sDBS.