Ultrastructural and electrophysiological determination of the patency of monkey cone outer segment membranes

Abstract

Cone photoreceptors support the high-acuity color vision characteristic of many primates, including humans. In several nonmammalian species, such as amphibians, the light-sensitive disk membranes within cone outer segments (COSs) are fully open to the extracellular space and continuous (patent) with the surrounding plasma membrane. In contrast, the extent of such patency in mammalian COSs has remained unresolved. The open disk architecture represents a fundamental distinction from the closed, discrete disks that dominate a rod OS (ROS), with important implications for outer-segment renewal and phototransduction. Here, we documented ROS and COS disk patency in the retina of macaque monkeys of both sexes, near the foveal-parafoveal boundary, by 3D ultrastructural analysis, using serial-section electron microscope tomography. The frequency of disk patency was determined at different locations along the entire OS length. It was less in the apical region of both COSs and ROSs, although still evident, even in ROSs. We complemented our 3D ultrastructural assessment of COS disk patency with electrophysiological measurements of whole-cell membrane capacitance. Both methods indicated that only a minority of all COS disk membranes are open, though more than in ROSs. Thus, in contrast to COSs of many lower vertebrates, the majority of monkey COSs are closed, especially distally. Compared with fully open disks, this structural organization should improve the efficiency of disk membrane renewal and may influence aspects of visual signaling. Significance Statement For over 60 years, scientists have debated whether the membrane disks of mammalian cone photoreceptors are continuous with the plasma membrane, as in many other vertebrates, or instead form closed, independent structures similar to those in rod photoreceptors. The difference between the two types of disk organization may have important implications for cell biological processes (e.g. disk membrane renewal) and the physiology of phototransduction. We report that EM tomographic analyses of disk ultrastructure and measurements of electrical membrane capacitance both indicate that the majority of cone disks are completely closed. This information now allows for enhanced understanding of the relationship between structure and function of cone photoreceptors – the sensory cells that mediate the most complex information about our external environment.