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Robert Lionel Seilheimer, Fan Gao, Samuel Wu; A Biophysical Model of the Photoreceptor Network in the Tiger Salamander Retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5512.
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© ARVO (1962-2015); The Authors (2016-present)
In addition to voltage-dependent currents in the inner segment, rod responses are shaped by electrical coupling with adjacent rods. While the physiology of single rods has been studied extensively, the function of the coupled rod network has not been systematically characterized. In this study we investigate the photoreceptor network with dual cell voltage clamp experiments and simulations using a quantitative biophysical model.
Tiger salamander retinas were whole-mounted and two adjacent rods were voltage-clamped. Recordings were made using an Axon Instruments Multiclamp 700A. One rod was stepped through a set of voltages while the other was clamped at its resting potential. Ionic currents were blocked pharmacologically using TEA, Cs+, and Co2+. Simulations were performed in MATLAB using custom-written software. Voltage-dependent ion currents (Ih, IKx, IKv, ICa, and Ileak) were modeled using Hodgkin-Huxley-like equations. The rod network was modeled as a square array coupled by linear, symmetric resistors using the measured conductance values.
Membrane currents of rod pairs were measured by dual whole-cell voltage clamp techniques. We found that rods in the flat-mounted salamander retina are strongly coupled with a mean junctional conductance of 1100 pS. We created a quantitative biophysical model of a coupled rod network incorporating the measured coupling conductance as well as voltage-gated currents such as Ih, Ikx, Ikv, and ICa. Using this model, we performed simulations of the dual voltage clamp experiments and our results were consistent with the experiments. To verify the model, we performed additional experiments in which one or more voltage-dependent currents were blocked pharmacologically. Our model adequately predicted the changes in the current waveform caused by this blockade.
Our results demonstrate the importance of electrical coupling between rods in shaping rod signals. Furthermore, our quantitative, biophysical model of the coupled rod network serves as a useful tool for predicting the behavior of the rod network. This will in turn allow us to better understand how inputs from the photoreceptor layer are transmitted to bipolar cells, retinal ganglion cells, and the rest of the visual system.
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