Figure 1.

Capacitive sensing currents are inherent to the function of voltage sensor domain (VSD)-based fluorescent protein (FP) voltage sensors. (A) Principal topology of voltage-sensitive fluorescent proteins (VSFPs): a voltage sensor comprising four transmembrane segments (S1–S4) is linked at its C-terminal end to a FP reporter domain consisting of either a single or a pair of fluorescent proteins. (B) Schematic illustration of the membrane charge distribution emphasizing the depolarization-induced translocation of S4 sensing charge from the cytosolic to the extracellular side together with the change of ionic surface charge. (C) Electrical equivalent circuit of a patch of neuronal membrane including a dynamic sensing capacitance, C_VSFP, to account for the sensing currents of VSFP membrane proteins. C_m is the linear membrane capacitance, G_i represents active membrane conductances with reversal potentials E_i (i = Na⁺, K⁺, Cl⁻, Ca²⁺), G_leak the membrane leak conductance with reversal potential E_leak.