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M. G. Grillo, P. Koulen; Control of Ryanodine Receptor Mediated Calcium Signaling by Calsenilin in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1877.
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Calsenilin, also known as KCHIP 3 and DREAM, is a calcium binding protein with a diversity of functions including transcriptional regulation, A-type potassium channel modulation, and presenilin processing. Recently calsenilin expression has been detected in rodent and primate retina. Ryanodine receptors (RyR) are intracellular calcium induced calcium release channels located on intracellular calcium stores and are involved in various signaling pathways. All three RyR subtypes have been observed in the retina. Changes in intracellular calcium mediated by RyRs control neuronal functions including ontogenesis, neurotransmission and cell death in physiologyical and pathophysiological states. In the brain, calsenilin expression levels affect both neuronal survival and intracellular calcium levels.
The expression and localization of RyR and calsenilin was determined with immunochemistry in mouse retina neurons. Functional effects of the interaction of RyRs and calsenilin were analyzed with single channel electrophysiology.
RyR and calsenilin were co-localized intracellularly in retina neurons most notably retinal ganglion cells. Binding of calsenilin to the cytosolic face of the RyR had a biphasic effect on RyR activity. At resting cytosolic calcium levels mean current and open probability of the RyR were attenuated while at higher cytosolic calcium levels mean current and open probability of the RyR were significantly potentiated.
Data from the present study suggest that calsenilin has the potential to control the intracellular Ca2+ concentration in retinal neurons through direct interaction with RyRs. Furthermore, the direct interaction of calsenilin and the intracellular calcium induced calcium release channels appears capable of influencing the gain of Ca2+ signaling pathways indicating potential roles in retina physiology, pathophysiology and neuroprotection.
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