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Oleg Yarishkin, Maxim B. Kozhemyakin, Daniel A. Ryskamp, David Krizaj; TRPV4 AUGMENTS THE EXCITABILITY OF MOUSE RETINAL GANGLION CELLS. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3579.
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© ARVO (1962-2015); The Authors (2016-present)
Neuronal expression of a polymodal non-selective cation channel Trpv4 (transient receptor potential isoform 4) in the mouse retina is largely limited to retinal ganglion cells (RGCs) where this channel might transduce swelling, temperature, polyunsaturated fatty acid and mechanical stimuli. Here we investigate whether and how Trpv4 integrates different sensory modalities and what effect such sensory transduction might have on RGC excitability.
Transmembrane currents and voltage responses were recorded in whole cell or cell-attached patch clamp configurations in acutely dissociated RGCs and in retinal wholemount preparations in the presence/absence of synaptic blockers and selective Trpv4 channel modulators. High-speed pressure clamp was used to apply defined pressure steps and ramps. Long-term effects of channel stimulation were assessed in the presence of Live/Dead (EtHD), RGC (Tuj-1) and gliotic (GFAP; Iba1) markers.
The selective Trpv4 agonist GSK1016790A induced large inward currents at the EC50, shifting the membrane potential of RGCs to depolarized values. This was associated with a decrease in the interspike interval and reduction in the spiking threshold observed during injection of positive current. These effects were observed in acutely dissociated RGCs as well as in retinal wholemount preparations and were antagonized by HC067047, a selective Trpv4 blocker. Concomitant stimulation with GSK1016790A, temperature (37oC), hypotonic swelling and/or pressure steps (5-50 msec; 5-50 mm Hg) augmented the excitatory effect on TRPV4 channel activation as well as facilitated light-evoked responses of ON and OFF RGCs.
Our results demonstrate that Trpv4 is capable of polymodal and additive integration of diverse sensory inputs at the RGC plasma membrane. Moreover, they show how intrinsic channels work together with synaptic inputs to modulate the excitability and mechanical thresholds, which regulate RGC firing and thus retinal output.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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