Figure 2. The depolarizing sag in ipRGCs and its mediation by I _h.

A–D) Analysis of the hyperpolarizations evoked in ipRGCs by current injections of 0, ⁻10, ⁻20, ⁻40 and ⁻60 pA (500 ms). For larger current steps, membrane potential sagged from its peak hyperpolarization back toward resting potential (Panels A and C; ‘Control’). A) Depolarizing sag in an example cell (top) and its blockade (bottom) by bath application of the I _h blocker ZD7288 (100 µM). B) Current-voltage plots of data in A drawn from the end of the current pulse, at the time marked by symbols in A (squares: control conditions; triangles: in presence of drug). Input resistance (R_N), calculated as the slope of the linear fit to these current-voltage data, was increased by the I _h antagonist. C, D) Extracellular Cs⁺ (3 mM), an alternative I _h blocker, reproduced the effects of ZD7288 in another ipRGC, blocking the depolarizing sag (C) and increasing R_N (D). Resting potential was maintained at ⁻72 mV in both this cell and that in A (see methods). E, F) Group data showing that both ZD7288 and Cs⁺ dramatically attenuate the depolarizing sag (E; measured as the peak-to-steady state potential difference during ⁻60 pA current injections) and increase R_N (F; measured as in B and D). * P<0.05.