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M. J. Van Hook, D. M. Berson; Hyperpolarization-Activated Cation Current (Ih) in ipRGCs. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1859.
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Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and drive non-image-forming responses to light. Little is known about the voltage-activated currents expressed by these cells and their roles in non-image-forming vision. Here, we characterize the hyperpolarization-activated cation current (Ih) in rat ipRGCs.
We selectively labeled ipRGCs by retrograde transport of rhodamine-labeled microspheres from the suprachiasmatic nuclei of rats. After papain dissociation, labeled cells were targeted for whole cell recording. Drugs were bath-applied.
We recorded from 106 ipRGCs, identified by retrolabeling and by light-evoked inward currents (mean 63 ± 39 pA). Nearly all of these ipRGCs (98/106; 92%) exhibited electrophysiological responses characteristic of the hyperpolarization-activated cation current Ih - a gradual depolarizing "sag" in response to hyperpolarizing current injection and/or a slowly developing inward current upon hyperpolarization of the membrane (activation time constant 891 ± 464 ms; n=11). Both the depolarizing sag and the slow inward current were blocked by Ih blockers Cs+ (3 mM) or ZD7288 (100 µM). Tail current analysis revealed that the fully activated Ih reversed at -43 ± 11mV, giving a relative Na:K permeability ratio of 0.16 ± 0.09 (n=8). Activation curves showed that Ih in ipRGCs has a threshold near -83 mV, V1/2 of -102 ± 9 mV and a slope factor of 6.3 ± 1.2 (n=12). Neither ZD7288 nor Cs+ affected the ipRGC membrane potential.
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