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

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.