2-aminoethoxydiphenylborane is an acute inhibitor of directly photosensitive retinal ganglion cell activity in vitro and in vivo

S Sekaran, G S Lall, K L Ralphs, A J Wolstenholme, R J Lucas, R G Foster, M W Hankins

Research output: Contribution to journalArticle

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Abstract

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.
Original languageEnglish
Pages (from-to)3981-3986
Number of pages6
JournalJournal of Neuroscience
Volume27
Issue number15
DOIs
Publication statusPublished - 2007

Fingerprint

Retinal Ganglion Cells
Ion Channels
Transient Receptor Potential Channels
Pupil
Reflex
Light Signal Transduction
Inositol 1,4,5-Trisphosphate Receptors
Light
Gene Knockout Techniques
Neuronal Plasticity
Ganglia
Retina
In Vitro Techniques
2-aminoethoxydiphenylborane
melanopsin

Cite this

Sekaran, S., Lall, G. S., Ralphs, K. L., Wolstenholme, A. J., Lucas, R. J., Foster, R. G., & Hankins, M. W. (2007). 2-aminoethoxydiphenylborane is an acute inhibitor of directly photosensitive retinal ganglion cell activity in vitro and in vivo. Journal of Neuroscience, 27(15), 3981-3986. https://doi.org/10.1523/jneurosci.4716-06.2007

2-aminoethoxydiphenylborane is an acute inhibitor of directly photosensitive retinal ganglion cell activity in vitro and in vivo. / Sekaran, S; Lall, G S; Ralphs, K L; Wolstenholme, A J; Lucas, R J; Foster, R G; Hankins, M W.

In: Journal of Neuroscience, Vol. 27, No. 15, 2007, p. 3981-3986.

Research output: Contribution to journalArticle

Sekaran, S, Lall, GS, Ralphs, KL, Wolstenholme, AJ, Lucas, RJ, Foster, RG & Hankins, MW 2007, '2-aminoethoxydiphenylborane is an acute inhibitor of directly photosensitive retinal ganglion cell activity in vitro and in vivo', Journal of Neuroscience, vol. 27, no. 15, pp. 3981-3986. https://doi.org/10.1523/jneurosci.4716-06.2007
Sekaran, S ; Lall, G S ; Ralphs, K L ; Wolstenholme, A J ; Lucas, R J ; Foster, R G ; Hankins, M W. / 2-aminoethoxydiphenylborane is an acute inhibitor of directly photosensitive retinal ganglion cell activity in vitro and in vivo. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 15. pp. 3981-3986.
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AU - Ralphs, K L

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AU - Lucas, R J

AU - Foster, R G

AU - Hankins, M W

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AB - 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.

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