Differentially Distributed IP₃Receptors and Ca²⁺Signaling in Rod Bipolar Cells

Abstract

The differential distribution of IP3Rs is used by rod bipolar cells to convey Ca2+ signals that are distinct in their duration, amplitude, and kinetics at the subcellular level, and that serve the functions of individual subcellular compartments. IP3R-mediated Ca2+ signaling indicates a potential mechanism for the adaptation of the ON-pathway of vision and for coincidence and threshold detection in retinal neurons.

Differential subcellular Ca2+ signaling in a highly specialized subpopulation of astrocytes

“…The diffuse punctate staining pattern is characteristic of cytosolic and ER localization, as seen for IP 3 R1 in other cell types (Kaja, et al, 2011, Medina-Ortiz, et al, 2007). In contrast, IP 3 R2 immunoreactivity was very strong in the nuclear envelope, consistent with reports for other cell types (Kaja, et al, 2011, Koulen, et al, 2005, Leite, et al, 2003, Medina-Ortiz, et al, 2007). This is the first description of such a molecular substrate of differential subcellular Ca 2+ signaling in astrocytes.…”

“…In neuronal cells, IP 3 Rs show a distinct expression profile with type 1 and type 3 expressed in the ER, while type 2 IP 3 Rs preferentially localize in the membranes of the nuclear envelope (Kaja, et al, 2011, Koulen, et al, 2005, Leite, et al, 2003). Our detailed subcellular quantification of Ca 2+ transients, which showed significantly larger nuclear vs. cytosolic/ER transients, consistent with stronger IP 3 R2 expression in the nucleus.…”

“…Furthermore, time to threshold was faster for nuclear vs. cytosolic transients. In this context it is important to note that IP 3 R2 possesses the highest ligand affinity of all IP 3 R subtypes, activating at concentrations well below those needed for IP 3 R1 and IP 3 R3 (Koulen and Thrower, 2001, Koulen, et al, 2005, Leite, et al, 2003) and while IP 3 R1 shows a pronounced inhibition by higher Ca 2+ concentrations, IP 3 R2 do not inactivate as readily under conditions of prolonged high cytosolic Ca 2+ concentrations (Koulen and Thrower, 2001). We have previously reported the selective up-regulation of IP 3 R2 under conditions of oxidative stress in neuronal HT-22 cells (Kaja, et al, 2011) indicating that the high physiological relevance of IP 3 R2 for normal ONHA Ca 2+ signaling could become even more pronounced under disease conditions associated with oxidative stress.…”

Effects of Presynaptic Mutations on a Postsynaptic Cacna1s Calcium Channel Colocalized with mGluR6 at Mouse Photoreceptor Ribbon Synapses

“…40 However, we found no specific enrichment of RyRs in ON-bipolar cell dendritic tips, as also observed in other studies. 44,45 Hence, the Ca v 1.1 channel is unlikely to act as a voltage sensor for ryanodine receptors in this context. Cacna1s/Ca v 1.1 plays an additional adaptive role in muscle fibers, because VDCC activity is greatly enhanced via phosphorylation after repetitive stimulation.…”

Microfluorimetry defines early axonal damage in a rat model of optic neuritis: A novel method targeting early CNS autoimmunity

“…In 1967, microfluorimetry was used to measure endogenous fluorescence in tissues as they were moved by a mechanical drive past a slit occluder positioned in the fluorescence microscope's light path (Van Orden et al, 1967). Following early experiments which probed the sensitivity of microfluorimetric detection, it remained relatively obscure and unchanged until the advent of its use to monitor electronic cell sorting in the late 1970s (Campbell et al, 1977;Yataganas et al, 1975), and the advent of its use for monitoring intracellular calcium flux in the late 1980s (Schlegel et al, 1987), and these remain the principal uses of microfluorimetric methods (Koulen et al, 2005;Murchison and Griffith, 2007). Microfluorimetric methods used in the present study took full advantage of modern digital image capture hardware and modern digital image analysis software to introduce large-area tissue microfluorimetry, a novel adaptation of existing methods which substantially increases the sensitivity of microfluorimetric assays by allowing the size of the immunohistochemically labeled tissue samples which can be analyzed to increase by more than two orders of magnitude.…”