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Tejinder Kaur, Scott A. Nawy; Trpm1 Desensitization Drives Transient Signaling In The On Pathway Of The Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4125.
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© ARVO (1962-2015); The Authors (2016-present)
Light depolarizes retinal ON bipolar cells by inactivating the mGluR6 signaling cascade and opening the synaptic non-selective cation channel, TrpM1. An accumulation of Ca2+ in these cells, either due to prolonged light stimulation or Ca2+ release from internal stores, results in desensitization of the transduction channel. One immediate consequence of desensitization is repolarization of the membrane and a reduction of transmitter release onto postsynaptic ganglion cells. Here, we show that desensitization in On bipolar cells provides a mechanism for conversion of sustained to transient signaling in ON ganglion cells. Furthermore, we test the hypothesis that the rate of extrusion of Ca2+ by pumps defines the rate-limiting step for recovery from desensitization.
Whole-cell voltage clamp recordings were made from bipolar and ganglion cells in acute tiger salamander retinal slices. Slices were bathed in the mGluR6 agonist L-AP4 to keep the transduction channel in On bipolar cells closed, mimicking darkness. Responses were evoked by depolarizing On bipolar cells with mGluR antagonist LY341495, mimicking light. Blockers of Ca2+ pumps and Na+/Ca2+ exchangers were added either in the bath or recording pipette.
Recordings from ON bipolar cells reveal that desensitization of Trpm1 reduces the steady state synaptic response to approximately 33% of the peak response with a time constant of about 900 ms. Recovery from desensitization depended on stimulus strength, with a time constant of 25 s for the strongest stimuli. Synaptic release from ON bipolar cells was monitored by recording EPSCs in downstream ganglion cells. Desensitization reduces the rate of vesicles released by approximately 50% at steady state (999±203 and 1948±278 vesicles/s, with and without desensitization, respectively). This decrease in the magnitude of vesicles released abolished spike train activity in ganglion cells.
Ca2+-dependent desensitization of TrpM1 limits the duration of signaling in the inner retina. Experiments currently underway will determine the role of Ca2+ extrusion/sequestration in setting the rate of recovery from desensitization.
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