Purchase this article with an account.
A. Payne, S. Kaja, P. Koulen; Control of Ryanodine Receptor Mediated Calcium Signaling by Presenilins in Mouse Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1876.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Ca2+ homeostasis and intracellular Ca2+ release are tightly controlled and contribute to a variety of cellular and synaptic functions in the neural retina. While in the invertebrate retina, ryanodine receptors (RyRs) have been described to contribute to light adaptation processes, little is known about their role in the mammalian retina, especially in retinal ganglion cells (RGCs), which are pivotal for information processing and signal integration and are affected by neurodegenerative diseases of the eye. The goal of the present study was to determine the regulatory role of presenilins for RyR mediated calcium signaling in the mouse RGCs.
Immunofluorescence studies were performed to determine the expression and localization of RyR and presenilins in isolated mouse RGCs and in vivo. Control of presenilins over RyR-mediated Ca2+ release from intracellular stores was measured using optical imaging techniques and single channel electrophysiology.
Immunocytochemical analyses revealed a distinct subcellular distribution of RyRs in RGCs and a co-distribution with presenilins. Addition of presenilins to the cytosolic face of the RyR resulted in a significant potentiation of RyR activity. The channel properties and Ca2+ dependence of the RyR were maintained while mean current and open probability were significantly potentiated in the presence of presenilins.
Our results indicate that RyRs and presenilins are co-expressed in RGCs, that they interact through direct binding and that their interaction results in the potentiation of intracellular Ca2+ release and Ca2+ induced Ca2+ release. As such, this interaction controlling the gain of intracellular Ca2+ release mechanisms represent a suitable pharmacological target in diseases of the retina involving Ca2+ dyshomeostasis.
This PDF is available to Subscribers Only