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David Boinagrov, Susanne Pangratz-Fuehrer, Su Hyun Kim, Natasha A. Naik, Keith Mathieson, Daniel Palanker; Upper Threshold of Extracellular Stimulation in Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4956. doi: https://doi.org/.
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To test a recent theoretical prediction of the existence of an upper threshold in extracellular stimulation, above which the action potential cannot be elicited , we characterized responses of retinal ganglion cells (RGC) in a broad range of stimuli strengths and durations using patch clamp technique.
The whole-cell and cell-attached recordings were obtained from RGCs of rat retina in vitro. Stimulation with monophasic current pulses of 0.01 - 5 ms duration was applied at 1 Hz repetition rate, via a micro-pipette positioned near the RGC.
At all pulse durations a short latency spike could be elicited at stimulus amplitudes exceeding the corresponding lower threshold. However, at stimuli exceeding the upper stimulation threshold the short-latency action potential could not be produced (see Figure). The upper threshold was clearly observed only at stimuli shorter than chronaxy (~ 0.5 ms). Ratio of the upper to lower stimulation thresholds varied with pulse duration and from cell to cell in the range of 1.5 to 12. At stimuli exceeding the upper threshold cellular hyperpolarization with slow (tens of ms) recovery was observed.
These results indicate the existence of the upper stimulation threshold, above which the action potential cannot be elicited. Upper limit of cellular stimulation and hyperpolarization above it are due to current reversal (outflow of the sodium ions) at trans-membrane voltages exceeding the sodium channel reversal potential. Boinagrov D, Loudin J, Palanker D. Strength-duration relationship for extracellular neural stimulation: numerical and analytical models. J Neurophysiol 104: 2236-2248, 2010.
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