Journal of Neurophysiology, Vol 51, Issue 1 164-182, Copyright © 1984 by APS

ARTICLES

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

E. A. Newman and L. L. Odette

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 Muller 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 Muller cell membrane, 5) spatial variations in the tortuosity factor and the volume fraction of extracellular space, 6) an extraretinal shunt resistance. Muller 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, Muller 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 Muller 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 Muller 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 Muller cell responses can be generated according to the K+ hypothesis: by passive Muller cell depolarization driven by variations in [K+]o.

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