June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
TRP channel-mediated integration of temperature, mechanical stress and glutamatergic stimuli in retinal ganglion cells
Author Affiliations & Notes
  • David Krizaj
    Ophthalmology& Visual Sciences, University of Utah, Salt Lake City, UT
    Neurobiology & Anatomy, University of Utah, Salt Lake City, UT
  • Daniel A Ryskamp
    Ophthalmology& Visual Sciences, University of Utah, Salt Lake City, UT
  • Micah Frerck
    Bioengineering, University of Utah, Salt Lake City, UT
  • Richard Rabbit
    Bioengineering, University of Utah, Salt Lake City, UT
  • Rene C Renteria
    Ophthalmology, University of Texas San Antonio, San Antonio, TX
  • Maxim Kozhemyakin
    Ophthalmology& Visual Sciences, University of Utah, Salt Lake City, UT
  • Footnotes
    Commercial Relationships David Krizaj, None; Daniel Ryskamp, None; Micah Frerck, None; Richard Rabbit, None; Rene Renteria, None; Maxim Kozhemyakin, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4378. doi:
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      David Krizaj, Daniel A Ryskamp, Micah Frerck, Richard Rabbit, Rene C Renteria, Maxim Kozhemyakin; TRP channel-mediated integration of temperature, mechanical stress and glutamatergic stimuli in retinal ganglion cells . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4378.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To characterize the molecular mechanism of temperature and mechanosensation and calcium homeostasis in retinal ganglion cells (RGCs) and place it within the context of RGC output signaling using a combination of biophysical, electrophysiological, genetic and physiological approaches.

Methods: RGCs were loaded with Ca indicator dyes (Fura-2, OGB-1, Fluo-4) and exposed to rapid increases water temperature (mediated by 1865 nm lasers) or slow (30-60 sec) elevations in bath temperature, or uniaxial/biaxial substrate stretch. Transmembrane currents were recorded directly with the whole cell patch and/or high-speed pressure clamp technique. Calcium signals were recorded with the confocal microscope, two photon micorscope or CCD cameras.

Results: Short 7 msec infrared pulses at 13.93-22.28 J/cm2, increased local bath temperature by 9-14 deg C and evoked robust and reproducible Ca elevations in wild type HEK293 cells. These responses were observed in the absence of external Ca2+ and were susceptible to the blockers of Ca2+ sequestration/release from the endoplasmic reticulum. An additional Ca2+ component, characterized by rapid temperature-dependent [Ca2+]i kinetics was observed in cells overexpressing TRPV4 channels and in RGCs. Heat-evoked Ca2+ elevations in RGCs were suppressed by Ruthenium Red (non-selective TRP channel blocker) and HC-067047 (selective TRPV4 antagonist) whereas heat -induced responses from stores comprised a minor component of the neuronal thermo-response. Moderate heat, membrane stretch and TRPV4 agonists facilitated NMDA receptor-mediated responses of RGCs. Consistent with this, an increase in bath temperature to 37°C increased the firing rate of RGCs, an effect that was inhibited by the TRPV4 blocker.

Conclusions: We conclude that force- and temperature-sensitive calcium influx through TRPV4 provides a depolarizing drive that modulates RGC excitability and thus retinal output to the visual brain. Our data further suggests that channels intrinsic to RGCs play a potentially important function by integrating the effects of non-visual inputs such as mechanical stimuli, temperature and vanilloid/cannabinoid agonists with light inputs derived through rod and cone circuits.

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