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Steven Hughes, Russell Foster, Stuart Peirson, Mark Hankins; Expression of 2PK+ leak channels in ganglion cells of the mouse retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6342. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Tandem pore domain potassium leak channels (2PK+) perform essential roles in setting resting membrane potential and levels of cellular excitability. To date the expression and functional role of 2PK+ channels in retinal ganglion cells (RGCs) of the retina has not been investigated. The aims of this study are to determine the levels of 2PK+ channel expression present in the mouse retina, and gain an improved understanding of the mechanisms that regulate resting membrane potential and cellular excitability of RGCs.
qPCR and ICC analysis were used to investigate the expression and distribution of 2PK+ channels in the mouse retina. Double labeling with retinal cell markers was used to confirm the expression of 2PK+ channels in specific cell types of the retina, including subtypes of RGCs. Whole cell patch clamp recordings from dissociated retinal cell cultures were used to record 2PK+ leak currents present in RGCs.
We confirm that multiple members of the 2PK+ channel family are expressed in the mouse retina. Based on qPCR analysis, TWIK-1, TRAAK, TASK-1 and TRESK are expressed at the highest levels, with lower expression detected for TWIK-2, TREK-1 and TASK-3. ICC analysis confirms the widespread expression of 2PK+ channels in the mouse retina, with TWIK-1, TWIK-2, TASK-1 and TREK-1 detected in Brn3a positive retinal ganglion cells and also within different subtypes of melanopsin expressing pRGCs. Using whole cell electrophysiology we confirm the presence of multiple 2PK+ type leak currents in RGCs.
We conclude that multiple members of the 2PK+ family of K+ leak channels are expressed in the mouse retina, and specifically within retinal ganglion cells. The distinct patterns of expression observed are consistent with the differential expression of these ion channels within distinct subtypes of retinal ganglion cells, including subtypes of pRGCs. It is likely therefore that these ion channels contribute to the different electrophysiological properties of RGC subtypes, and offer a range of mechanisms to influence the resting membrane potential and cellular excitability of these cells. The role of 2PK+ channels in neuroprotection is of significant interest and offers new potential targets for the treatment of retinal disease.
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