Localization of inositol 1,4,5‐trisphosphate receptors in mouse retinal ganglion cells

Mafe, O.A.; Gregg, Elaine V.; Medina-Ortiz, Wanda E.; Koulen, Peter

doi:10.1002/jnr.21090

Cited by 5 publications

(12 citation statements)

References 48 publications

(52 reference statements)

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“…3b and Fig. 3c have been attributed to cross-linking reactions and/or IP 3 R protein degradation 23 . As such, the quantification of IP 3 R protein expression in aorta and vena cava samples (figs.…”

Section: Resultsmentioning

confidence: 94%

Divergent signaling mechanisms for venous versus arterial contraction as revealed by endothelin-1

Tykocki

Jackson

et al. 2015

Journal of Vascular Surgery

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Objective Venous function is underappreciated in its role in blood pressure determination, a physiological parameter normally ascribed to changes in arterial function. Significant evidence points to the hormone endothelin-1 (ET-1) as being important to venous contributions to blood pressure. We hypothesized that the artery and vein should similarly depend on the signaling pathways stimulated by ET-1, specifically phospholipase C (PLC) activation. This produces two functional arms of signaling: diacylglycerol (DAG; protein kinase C activation) and inositol trisphosphate (IP3) production (intracellular calcium release). Methods The model was the male Sprague Dawley rat. Isolated tissue baths were used to measure isometric contraction. Western blot and immunocytochemical analyses measured the magnitude of expression and site of expression, respectively, of IP3 receptors in smooth muscle/tissue. Pharmacological methods were used to modify phospholipase C activity and signaling elements downstream of phospholipase C (IP3 receptors, protein kinase C). Results ET-1-induced contraction was phospholipase C-dependent in both tissues as the phospholipase C inhibitor U73122 significantly reduced contraction in aorta (86±4% of control, P<.05) and vena cava (49±11% of control, P<.05). However, ET-1-induced contraction was not significantly inhibited by the IP3 receptor inhibitor 2-APB (100 μM) in vena cava (82±8% of control, P=.23) but was in the aorta (55±4% of control, P<.05). All three IP3 receptor isoforms were located in venous smooth muscle. IP3 receptors were functional in both tissues as the novel membrane-permeable IP3 analogue (Bt-IP3; 10μM) contracted aorta and vena cava. Similarly, while the PKC inhibitor chelerythrine (10μM) attenuated ET-1-induced contraction in vena cava and aorta (5±2% and 50±5% of control, respectively; P<.05), only the vena cava contracted to the DAG analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG). Conclusions These findings suggest that ET-1 activates phospholipase C in aorta and vena cava, but vena cava contraction to ET-1 may be largely IP3-independent. Rather, DAG – not IP3 – may contribute to contraction to ET-1 in vena cava, in part by activation of protein kinase C. These studies outline a fundamental difference between venous and arterial smooth muscle and further reinforce a heterogeneity of vascular smooth muscle function that could be taken advantage of for therapeutic development.

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Section: Resultsmentioning

confidence: 94%

Divergent signaling mechanisms for venous versus arterial contraction as revealed by endothelin-1

Tykocki

Jackson

et al. 2015

Journal of Vascular Surgery

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“…RGCs were prepared from 4–6 weeks old male albino Swiss Webster mice (6 retinae from three different animals per preparation) and cultured as described by us previously (Mafe et al, 2006). Briefly, eyes were enucleated and dissected in Neurobasal A medium (Invitrogen, Carlsbad, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Immunocytochemistry was carried out as described by us previously for RGCs (Mafe et al, 2006). Briefly, after 7–14 days of culture, RGCs were fixed using 4% paraformaldehyde in 10 mM phosphate buffered saline pH 7.4 (PBS) for 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…Immunohistochemistry was carried out essentially as previously described (Koulen and Brandstatter, 2002, Kaja et al, 2003, Koulen et al, 2005a, Mafe et al, 2006). Eye cups were immersion fixed in 4% paraformaldehyde in PBS for 20 min.…”

Section: Methodsmentioning

confidence: 99%

“…Recent progress has been made in elucidating the signaling pathways in RGC dendrites involving voltage-gated Ca 2+ channels (Margolis et al, 2010), however, surprisingly little is known about expression, distribution and function of intracellular Ca 2+ channels in RGCs. We previously reported the differential distribution of IP 3 Rs in RGCs (Mafe et al, 2006), and polycystin-L and polycystin-2L2 were detected in retina (Nomura et al, 1998, Wu et al, 1998, Guo et al, 2000). The lack of knowledge on the role of polycystin-2 in the retina is surprising given the tentative association between polycystic kidney disease and macular defects in patients and experimental models (Narendran et al, 2004, Feng et al, 2009).…”

Section: Introductionmentioning

confidence: 98%

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Distribution and function of polycystin-2 in mouse retinal ganglion cells

et al. 2012

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The polycystin family of transient receptor potential (TRP) channels form Ca2+ regulated cation channels with distinct subcellullar localizations and functions. As part of heteromultimeric channels and multi-protein complexes, polycystins control intracellular Ca2+ signals and more generally the translation of extracellular signals and stimuli to intracellular responses. Polycystin-2 channels have been cloned from retina, but their distribution and function in retinal ganglion cells (RGCs) have not yet been established. In the present study, we determined cellular and subcellular localization as well as functional properties of polycystin-2 channels in RGCs. Polycystin-2 expression and distribution in RGCs was assessed by immunohistochemistry on vertical cryostat section of mouse retina as well as primary cultured mouse RGCs, using fluorescence microscopy. Biophysical and pharmacological properties of polycystin-2 channels isolated from primary cultured RGCs were determined using planar lipid bilayer electrophysiology. We detected polycystin-2 immunoreactivity both in the ganglion cell layer as well as in primary cultured RGCs. Subcellular analysis revealed strong cytosolic localization pattern of polycystin-2. Polycystin-2 channel current was Ca2+ activated, had a maximum slope conductance of 114 pS and could be blocked in a dose-dependent manner by increasing concentrations of Mg2+. The cytosolic localization of polycystin-2 in RGCs is in accordance with its function as intracellular Ca2+ release channel. We conclude that polycystin-2 forms functional channels in RGCs, of which biophysical and pharmacological properties are similar to polycystin-2 channels reported for other tissues and organisms. Our data suggest a potential role for polycystin-2 in RGC Ca2+ signaling.

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Robust expression of the TRPC1 channel associated with photoreceptor loss in the rat retina

Caminos,

Murillo-Martínez,

García-Belando

et al. 2023

Experimental Eye Research

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Localization of inositol 1,4,5‐trisphosphate receptors in mouse retinal ganglion cells

Cited by 5 publications

References 48 publications

Divergent signaling mechanisms for venous versus arterial contraction as revealed by endothelin-1

Divergent signaling mechanisms for venous versus arterial contraction as revealed by endothelin-1

Distribution and function of polycystin-2 in mouse retinal ganglion cells

Robust expression of the TRPC1 channel associated with photoreceptor loss in the rat retina

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