Schematic representation of the proposed mechanism taking place during GO (a) and rGO (b) stimulation and of the consequent cellular response. Upper panels: a, In the case of GO, charge accumulation at the GOcell interface (1) causes depolarization of the membrane, which promotes opening of VGCCs or TRPA1 and EXT-Ca 2+ influx (2). 3, Ca 2+ entry leads to calcium-induced calcium release via IP 3 or SERCA but not RyR. 4, The IP 3 path potentiates the Ca 2+ influx mediated by TRPV4 via the calcium-induced calcium increase mechanism 13 , 57 . The entrance of further external Ca 2+ into the cell causes a steady increase of cytoplasmic Ca 2+ (S-type signal). TRPA1 might be involved in this process as a cooperative channel promoting either maintenance of basal Ca 2+ levels or potentiation of the Ca 2+ influx over time 25 , 56 . IP 3 Rs, IP 3 receptors. Lower panels: the potential drop across the substrate (GO, a, and rGO, b), and the direction of electric fields created by the potential applied to the substrate (E sub). The electric fields created on the cell walls by the membrane potential (E mem), pointing inside the cell, are also shown. Bottom panel: the scheme of the equivalent electric circuit, as described in the text.
