Hyperpolarization-Activated Current (Ih) in Ganglion-Cell Photoreceptors

Matthew J Van Hook,David M Berson,William Rowland Taylor

doi:10.1371/journal.pone.0015344

Matthew J Van Hook, David M Berson + Show 1 more

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https://doi.org/10.1371/journal.pone.0015344

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Journal: PloS one	Publication Date: Dec 20, 2010
Citations: 91	License type: CC BY 4.0

Affiliation: Brown University, Providence College

Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and serve as the primary retinal drivers of non-image-forming visual functions such as circadian photoentrainment, the pupillary light reflex, and suppression of melatonin production in the pineal. Past electrophysiological studies of these cells have focused on their intrinsic photosensitivity and synaptic inputs. Much less is known about their voltage-gated channels and how these might shape their output to non-image-forming visual centers. Here, we show that rat ipRGCs retrolabeled from the suprachiasmatic nucleus (SCN) express a hyperpolarization-activated inwardly-rectifying current (I h). This current is blocked by the known I h blockers ZD7288 and extracellular cesium. As in other systems, including other retinal ganglion cells, I h in ipRGCs is characterized by slow kinetics and a slightly greater permeability for K+ than for Na+. Unlike in other systems, however, I h in ipRGCs apparently does not actively contribute to resting membrane potential. We also explore non-specific effects of the common I h blocker ZD7288 on rebound depolarization and evoked spiking and discuss possible functional roles of I h in non-image-forming vision. This study is the first to characterize I h in a well-defined population of retinal ganglion cells, namely SCN-projecting ipRGCs.

Highlights

Photosensitive retinal ganglion cells are a unique class of retinal output neurons distinguished by their expression of the photopigment melanopsin and their direct sensitivity to light [1,2]
Ih in ganglion-cell photoreceptors This study demonstrates the presence of the hyperpolarizationactivated current Ih in intrinsically photosensitive retinal ganglion cells
The observed current shares the basic characteristics of Ih in other cell types, namely a slow, inwardly-rectifying current activated by membrane hyperpolarization. It is blocked by the bradycardic agent ZD7288 and by extracellular Cs+ at millimolar concentrations

Summary

Introduction

Photosensitive retinal ganglion cells (ipRGCs) are a unique class of retinal output neurons distinguished by their expression of the photopigment melanopsin and their direct sensitivity to light [1,2]. They serve as the dominant or sole source of direct retinal influence on non-image-forming visual processes such as circadian photoentrainment, the pupillary light reflex, and suppression of melatonin production in the pineal [3,4,5]. M1 cells are the major source of retinal input to the suprachiasmatic nucleus of the hypothalamus (SCN), the central circadian pacemaker [7] Their dendrites stratify in outermost sublamina of the inner plexiform layer (IPL). Other ipRGC classes stratify in the inner layers of the IPL [8,9,10,11] and innervate an array of central targets including the superior colliculus, the olivary pretectal nucleus, posterior pretectal nucleus, and lateral geniculate nucleus [7,10]

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