A Photoreceptor Model Considering Regulation of Ionic Homeostasis

Abstract

Detailed photoreceptor model would be a powerful diagnostic tool for identification of pathological states in retina. Kamiyama model (1996) may reconstruct timecourse of the light-induced membrane current (Iphoto) and Ca2+ dynamics in photoreceptors. However, the model does not consider ionic homeostasis, except for Ca2+, and is incapable of simulating changes in concentrations of K+, Na+, and Cl-. Calculating these ionic concentrations is critically important since they indirectly control intracellular Ca2+, and thus ATP. On the basis of the Kamiyama model (1996), we propose a new model by elaborating ion channels and transporters. Specifically, Na+-K+-Cl- co-exchanger current was developed referring to Terashima (2006). Na+/Ca2+-K+ exchanger current was constructed based on Na+/Ca2+ exchanger current (Luo, 1994). Some current models in Kamiyama (1993), e.g. voltage dependent Ca2+ current, developed based on lizard or salamander photoreceptor were modified to mammalian cell-based models. For concentrations of K+, Na+ and Cl-, one compartment of each ion were assumed through the cell, whereas Ca2+ concentrations at outer (OS) and inner segment (IS) were separately calculated due to relatively slower diffusion property of Ca2+. Using the model, timecourses of the light-induced change in concentrations of Ca2+, K+, Na+ and Cl- were simulated. Upon light stimulation, decrease in Ca2+-and Na+-permeable Iphoto at the outer segment caused hyperpolarization and simultaneous decrease in [Na+]i and [Ca2+]OS. [K+]i and [Cl-]i were also reduced due to subsequently decrases in activities of Na+/K+pump and K+/Cl-exchanger, respectively. On the contrary, [Ca2+]IS was increased due to a rise in driving force for Ca2+ entry through leak channels duing hyperpolarization. However, membrane potential as well as ionic concentrations were all returned to the resting state when Iphoto was recovered from inhibition. The proposed model thus well maintained ionic homeostasis before and after light stimulations.