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The Journal of Neuroscience, April 11, 2007, 27(15):3981-3986; doi:10.1523/JNEUROSCI.4716-06.2007

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Brief Communications
2-Aminoethoxydiphenylborane Is an Acute Inhibitor of Directly Photosensitive Retinal Ganglion Cell Activity In Vitro and In Vivo

Sumathi Sekaran,¹ Gurprit S. Lall,² Katherine L. Ralphs,³ Adrian J. Wolstenholme,³ Robert J. Lucas,² Russell G. Foster,¹ and Mark W. Hankins¹

¹Circadian and Visual Neuroscience Group, University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, United Kingdom, ²Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom, and ³Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, United Kingdom

Correspondence should be addressed to Sumathi Sekaran, Circadian and Visual Neuroscience Group, University of Oxford, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK. Email: sumathi.sekaran{at}eye.ox.ac.uk

The mammalian retina contains directly photosensitive retinal ganglion cells (RGCs), which use the photopigment melanopsin. The generation of mice lacking melanopsin has been invaluable in elucidating the function of these cells. These animals display deficiencies in circadian photoentrainment, the pupil light reflex, and the circadian regulation of the cone pathway. Interpreting the results from such gene knock-out models is always complicated by neuronal plasticity and the potential for restructuring of neuronal networks. Until now, the study of photosensitive RGCs has lacked an acute inhibitor. 2-Aminoethoxydiphenylborane (2-APB) is an antagonist at IP₃ receptors and an inhibitor of canonical transient receptor potential ion channels (TRPCs). Here, we show that 2-APB is an extremely potent in vitro inhibitor of the photosensitive RGCs and that its effect is independent of store-dependent Ca²⁺ release. The identification of canonical TRPC6 and TRPC7 ion channels in melanopsin-expressing ganglion cells suggests that 2-APB may act directly on a TRPC ion channel. Importantly, using the pupil light reflex as a functional assay, we show that 2-APB inhibits photosensitive RGC activity in vivo. Collectively, our data further elucidate the phototransduction pathway in the photosensitive RGCs and demonstrate that 2-APB can be used to silence activity in these cells both in vitro and in vivo.

Key words: 2-aminoethoxydiphenylborane; melanopsin; retinal ganglion cell; TRPC6; TRPC7; pupil light reflex

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Received Oct. 30, 2006; revised March 12, 2007; accepted March 14, 2007.

Correspondence should be addressed to Sumathi Sekaran, Circadian and Visual Neuroscience Group, University of Oxford, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK. Email: sumathi.sekaran{at}eye.ox.ac.uk

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