Tension change in photoreceptor disk membranes due to early receptor potential causes contraction of the outer segment

Abstract

Purpose : Phase-resolved optical coherence tomography (pOCT) measurements of the optical path length (OPL) change in cone photoreceptor outer segments after a light stimulus (optoretinogram) demonstrate a fast, millisecond-scale contraction followed by a slow elongation, but the mechanism of this early response is unknown. We demonstrate that the voltage change across the outer segment disks during the early receptor potential (ERP) affects the membrane tension to an extent that explains the observed mechanical deformation.

Methods : Conformational changes in opsins after photoisomerization result in the fractional shift of charge across the disk membrane, leading to a transmembrane voltage change known as the ERP. Lateral repulsion of the ions on both sides of the membrane affect its surface tension and leads to its lateral expansion. We created an analytical model that combines the dynamics of the ERP, the voltage dependent membrane tension, and the mechanics of the folded lipid membrane. Measurements of the OPL changes in dark-adapted cone outer segments following a 1 ms flash stimulus were taken with a fast line-scan pOCT system in healthy volunteers.

Results : The amplitude of the fast response increases logarithmically with the number of incident photons up to 40 nm, and its peak shifts earlier at higher stimulus intensity, up to 2.5 ms. Both phenomena can be explained by increase of the membrane stiffness with increasing expansion due to flattening of the thermally-induced bending fluctuations at higher tension. Due to volume conservation at ms scale, the lateral expansion of the disk membranes leads to axial contraction of the outer segment. A few ms later, an influx of water due to an osmotic imbalance, created by metabolites of the phototransduction, leads to a slow increase in the outer segment volume, lasting hundreds of ms (Figure).

Conclusions : Our model of the fast contraction of the outer segment after stimulus provides a good match to experimental observations. The fast response is driven by the ERP, coupled to mechanical movement via the voltage-dependent membrane tension, with the deformations saturating at high light intensity due to a rapid increase of the membrane stiffness with expansion.

This is a 2020 ARVO Annual Meeting abstract.

 

Experimental data (solid line) and the model (dash line) of the outer segment deformation at two flash intensities.