Figure 1

Reaction scheme and model for the generation of photocurrent in human cones. A. Photopigment R is converted by light I into activated photopigment R*, which is inactivated with rate constant 1/τ_R. R* activates a G-protein (transducin) which subsequently forms an activated complex with PDE. The activated transducin-PDE complex is inactivated with rate constant 1/τ_E; it hydrolyses cGMP with rate constant β. CNG channels in the membrane, opened under control of cGMP, admit an ionic current I_chan, part of which is carried by Ca²⁺ ions. Ca²⁺, which is removed with rate constant 1/τ_Ca, regulates the production rate α of cGMP via guanylyl cyclase (GC). Ca²⁺ also exerts a direct inhibitory influence on the CNG channels. Part of the ionic current I_chan charges the membrane of the cone outer segment (with membrane time constant τ_m), and the remainder of I_chan flows into the cone inner segment. In the intact eye the extracellular flow of this circulating current produces an extracellular voltage drop, which is measured as the cone contribution to the ERG (as in Fig. 2). In single-cell experiments the extracellular flow of current may be measured using a suction pipette (as in Fig. 3). B. The boxes with τ_(·) represent first-order low-pass filters. The rate constant of cGMP hydrolysis consists of a dark rate constant, 1/τ_D, plus a light-dependent component with scaling determined by the gain factor k_β. The nonlinear differential equation describing cGMP hydrolysis can be understood as a static nonlinearity 1/β followed by a low-pass filter with time constant τ_β = 1/β [3]. The calcium feedback loop is governed by n_X, the apparent Hill coefficient of cGMP activation of the CNG channels (including the effect of a local calcium feedback, indicated by the dashed line), and by n_cyc, the Hill coefficient of GC deactivation; a_cyc is a scaling constant.