Model of electroretinogram b-wave generation: a test of the K+ hypothesis

Abstract

Generation of the electroretinogram b-wave is simulated with a computer model representing a dark-adapted amphibian retina. The simulation tests the K+ hypothesis of b-wave generation, which holds that b-wave currents arise from localized Müller cell depolarizations generated by light-evoked increases in extracellular K+ concentration, [K+]o. The model incorporates the following components and processes quantitatively: 1) two time-dependent K+ sources representing the light-evoked [K+]o increases in the inner and outer plexiform layers, 2) a time- and [K+]o-dependent K+ sink representing the [K+]o decrease in the rod inner segment layer, 3) diffusion of released K+ through extracellular space, 4) active K+ reuptake and passive K+ drift across the Müller cell membrane, 5) spatial variations in the tortuosity factor and the volume fraction of extracellular space, 6) an extraretinal shunt resistance. Müller cells are modeled with 1) cytoplasmic resistance, 2) spatial variations in membrane permeability to K+, and 3) a membrane potential specified by the Nernst equation and transmembrane current flow. For specified K+ source and sink densities, the model computes [K+]o variations in time and retinal depth. Based on these [K+]o distributions, Müller cell potentials, current source-density profiles, and intraretinal and transretinal voltages are calculated. Imposed [K+]o distributions similar to those seen experimentally during the b-wave lead to the generation of a transient b-wave response and to a prolonged Müller response in the model system. These response time courses arise because the b-wave is dominated by the short-lived distal [K+]o increase, while the Müller response primarily reflects the long-lived proximal [K+]o increase. Current source-density distributions and intraretinal voltage profiles that are generated by the model at the peak of the b-wave closely resemble experimental results. The model generates a realistic slow PIII potential in response to prolonged [K+]o decreases in the distal retina and reproduces the K+ ejection results of Yanagida and Tomita (50) accurately. Simulations also suggest that tissue damage caused by K+-selective micropipettes in experimental preparations can lead to an underestimation of the distal [K+]o increase. The simulations demonstrate that the spatiotemporal properties of intraretinal b-wave voltages and currents and Müller cell responses can be generated according to the K+ hypothesis: by passive Müller cell depolarization driven by variations in [K+]o.

Contribution of Membrane-Damaging Toxins to Bacillus Endophthalmitis Pathogenesis

“…Latent b-wave responses mark the initial events in retinal dysfunction and have been shown to occur in the early stages of degenerative retinal syndromes including diabetic retinopathy (7,40), retinitis pigmentosa (19), and retinal ischemia (6). b-wave function results from the flow of current from the photoreceptor cell layers of the retina into the vitreous via the Müller cell in response to a visual stimulus (33). The Müller cell, which spans the length of the retina, provides architectural support and regulates neurotransmitter levels in the retina by degrading or removing these substances during neuronal activity (36).…”

Potassium channel Kir4.1 macromolecular complex in retinal glial cells

“…Within the central nervous system (CNS) Kir4.1 is expressed in glia, including the principal glial cell type in the retina, the M€ uller cell (Kofuji et al, 2000). Kir4.1 is implicated in the process of ''potassium siphoning'' (Newman and Odette, 1984), a mechanism of potassium buffering that helps stabilize the extracellular potassium concentration ([K 1 ] o ) in the face of neuronallyderived ion fluxes (Amedee et al, 1997;Kofuji et al, 2000;Kofuji and Connors, 2003).…”

Control of Extracellular Potassium Levels by Retinal Glial Cell K + Siphoning

“…We have suggested that the retinal Müller cell, a specialized astrocyte that spans nearly the entire width of the retina, buffers changes in retinal [K + ] o (4,5). We have shown that amphibian Müller cells are almost exclusively permeable to K + (6) and that 94 percent of the total K + conductance in these cells occurs in the Müller cell endfoot, a process lying adjacent to the vitreous humor (4).…”