The role of voltage-gated ion channels in visual function and disease in mammalian photoreceptors

Pflugers Arch. 2021 Sep;473(9):1455-1468. doi: 10.1007/s00424-021-02595-2. Epub 2021 Jul 13.

Abstract

Light activation of the classical light-sensing retinal neurons, the photoreceptors, results in a graded change in membrane potential that ultimately leads to a reduction in neurotransmitter release to the post-synaptic retinal neurons. Photoreceptors show striking powers of adaptation, and for visual processing to function optimally, they must adjust their gain to remain responsive to different levels of ambient light intensity. The presence of a tightly controlled balance of inward and outward currents modulated by several different types of ion channels is what gives photoreceptors their remarkably dynamic operating range. Part of the resetting and modulation of this operating range is controlled by potassium and calcium voltage-gated channels, which are involved in setting the dark resting potential and synapse signal processing, respectively. Their essential contribution to visual processing is further confirmed in patients suffering from cone dystrophy with supernormal rod response (CDSRR) and congenital stationary night blindness type 2 (CSNB2), both conditions that lead to irreversible vision loss. This review will discuss these two types of voltage-gated ion channels present in photoreceptors, focussing on their structure and physiology, and their role in visual processing. It will also discuss the use and benefits of knockout mouse models to further study the function of these channels and what routes to potential treatments could be applied for CDSRR and CSNB2.

Keywords: KCNV2; Photoreceptors; Retinal degeneration; Voltage-gated calcium channels; Voltage-gated potassium channels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Cone Dystrophy / genetics
  • Cone Dystrophy / metabolism*
  • Eye Diseases, Hereditary / genetics
  • Eye Diseases, Hereditary / metabolism*
  • Genetic Diseases, X-Linked / genetics
  • Genetic Diseases, X-Linked / metabolism*
  • Humans
  • Myopia / genetics
  • Myopia / metabolism*
  • Night Blindness / genetics
  • Night Blindness / metabolism*
  • Photoreceptor Cells, Vertebrate / metabolism*
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism*
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / metabolism

Substances

  • Calcium Channels
  • Potassium Channels, Voltage-Gated

Supplementary concepts

  • Night blindness, congenital stationary
  • Retinal Cone Dystrophy 3A
  • Retinal Cone Dystrophy 3B