Intrinsic phototransduction persists in melanopsin-expressing ganglion cells lacking diacylglycerol-sensitive TRPC subunits

Authors

  • Claudio E. Perez-Leighton,

    1. Department of Neuroscience, University of Minnesota, 321 Church St SE, 6-145 Jackson Hall, Minneapolis, MN, USA
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    • C.E.P.-L. and T.M.S. contributed equally to this study.

  • Tiffany M. Schmidt,

    1. Department of Neuroscience, University of Minnesota, 321 Church St SE, 6-145 Jackson Hall, Minneapolis, MN, USA
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    • C.E.P.-L. and T.M.S. contributed equally to this study.

  • Joel Abramowitz,

    1. Laboratory of Neurobiology, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Building 101, Room F180, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA
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  • Lutz Birnbaumer,

    1. Laboratory of Neurobiology, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Building 101, Room F180, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA
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  • Paulo Kofuji

    1. Department of Neuroscience, University of Minnesota, 321 Church St SE, 6-145 Jackson Hall, Minneapolis, MN, USA
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Dr P. Kofuji, as above.
E-mail: kofuj001@umn.edu

Abstract

In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate various non-image-forming photic responses, such as circadian photoentrainment, pupillary light reflex and pineal melatonin suppression. ipRGCs directly respond to environmental light by activation of the photopigment melanopsin followed by the opening of an unidentified cation-selective channel. Studies in heterologous expression systems and in the native retina have strongly implicated diacylglycerol-sensitive transient receptor potential channels containing TRPC3, TRPC6 and TRPC7 subunits in melanopsin-evoked depolarization. Here we show that melanopsin-evoked electrical responses largely persist in ipRGCs recorded from early postnatal (P6–P8) and adult (P22–P50) mice lacking expression of functional TRPC3, TRPC6 or TRPC7 subunits. Multielectrode array (MEA) recordings performed at P6–P8 stages under conditions that prevent influences from rod/cone photoreceptors show comparable light sensitivity for the melanopsin-evoked responses in these mutant mouse lines in comparison to wild-type (WT) mice. Patch-clamp recordings from adult mouse ipRGCs lacking TRPC3 or TRPC7 subunits show intrinsic light-evoked responses equivalent to those recorded in WT mice. Persistence of intrinsic light-evoked responses was also noted in ipRGCs lacking TRPC6 subunits, although with significantly smaller magnitudes. These results demonstrate that the melanopsin-evoked depolarization in ipRGCs is not mediated by either TRPC3, TRPC6 or TRPC7 channel subunits alone. They also suggest that the melanopsin signaling pathway includes TRPC6-containing heteromeric channels in mature retinas.

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