Voltage-gated conductances increase the sensitivity of mouse rod photoresponses
following pigment bleaching

Abstract

Purpose : Light absorption by rhodopsin in rod photoreceptors initiates a phototransduction cascade which leads to changes in the rod photocurrent. This, in turn, creates a change in membrane potential (photovoltage) that is ultimately responsible for controlling glutamate release onto downstream retinal neurons. This photovoltage is further modulated by inner segment K⁺ conductances that filter the photocurrent. Here, we investigate the role that these voltage gated K⁺ conductances play in modulating sensitivity following bright light (bleaching) adaptation in mouse retina.

Methods : We used single cell suction electrode recording to measure photocurrent. Rod photovoltage was measured from retinal slices using current clamp recording and from trans-retinal ERGs. Recordings were made in dark adapted as well as in bleached retinae. The amount of bleaching was monitored by microspectrophotometry. Inner segment conductances were pharmacologically blocked, either by using a Cs⁺ internal solution, or by perfusion with a cation channel blocker (ZD-7288).

Results : Rod photocurrents evoked from bleached rods displayed desensitization and accelerated kinetics compared to dark-adapted rods. When the sensitivity following multiple bleaches were fitted with the Weber-Fechner function (S/S_DA=[1-F]/[1+kF], where S is sensitivity, F is fraction bleached rhodopsin and k a constant) we obtained a k value of 22 indicating desensitization far beyond what is predicted by loss in quantum catch alone. In contrast, photovoltage responses displayed less desensitization (k = 8) and slower response kinetics. When the inner segment conductances potassium were blocked by ZD-7288 or Cs⁺, the photovoltage of bleached rods displayed response kinetics and sensitivity similar to the photocurrent (k = 20).

Conclusions : Rod inner segment voltage-gated K⁺ conductances plays a role in regulating the rod output under bleach adapted conditions. These conductances decompress the voltage response that is compressed due to the low dark current in bleach adapted conditions. Our results are consistent with a model in which the sensitization of the photovoltage by rod inner segment conductances appears to allow rod vision to extend to higher light intensities than previously appreciated.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.