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D. Krizaj, W. Huang, J. Zou, C. Punzo, L. Birnbaumer, P. Barabas; The Canonical Trpc1 Channel Modulates Rod Signals in the Mammalian Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5177.
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© ARVO (1962-2015); The Authors (2016-present)
TRPC1 channels integrate signals between calcium stores, heterotrimeric G proteins and plasma membrane cation fluxes. Although these channels are ubiquitously expressed throughout the CNS, physiological roles for endogenous TRPC1 channels remain largely unknown. We examined expression and localization of TRPC1 mRNA and protein in the retinas of mouse, rat, rabbit, ground squirrel & macaque and determined function of these ion channels in visual signaling using TRPC1 knockout mice.
Retinas from wild type and TRPC1 knockout mice were investigated with in situ hybridization, quantitative PCR, immunohistochemistry, ERG recording and visual behavior tasks. Probes for TRPC1 were generated by sub-cloning part of the coding sequence into pGEMT-Easy vector; the identity of the gene was verified by sequence analysis. In qPCR, TRPC1 gene expression was normalized with GAPDH. ERG was recorded from anesthetized mice at 2-6 months of age. KOs were generated by inserting a PGK-neo casette with a Stop codon into the exon 8 of the TRPC1 gene.
TRPC1 accounted for ~15% of total canonical TRP transcript family in the mouse retina. The mRNA was localized to the outer and inner nuclear layers, with a moderate signal in the GCL. TRPC1 antibodies immunostained rodent rod, bipolar and ganglion cell perikarya; dense puncta were observed in processes in the IPL. The TRPC1 message was reduced 75% in retinas from 3 month old rd1 mice; there were no significant changes in TRPC1 expression in 1-15 month old DBA/2J mice. In response to flashes producing from ~0.012 to 5x10 exp6 Rh*/rod, the a-wave response in the KO was increased by 25% (P<0.05) with no change in the scotopic b-wave. No difference in the amplitude or kinetics of photopic ERG responses was observed between wt controls and retinas lacking TRPC1.
TRPC1 is expressed in rod photoreceptors, with additional localization to bipolar and ganglion neurons. Calcium fluxes through endogenous TRPC1s suppress rod signals, possibly through adaptation of the phototransduction cascade.
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