Differential Distribution of Inositol (1,4,5)-trisphosphate Receptor Isoforms Determines Ca2+ Signaling Patterns in Rod Bipolar Cells

Abstract

Abstract: : Purpose: Intracellular calcium channels, inositol (1,4,5)-trisphosphate receptors (IP3R) and ryanodine receptors (RyR) contribute substantially to cytosolic calcium concentration transients and thereby modulate neuronal function. We had previously identified the distribution of group I metabotropic glutamate receptors (mGluRs), signaling proteins upstream of intracellular calcium channels in rod bipolar cells of the mammalian retina (J Neurosci 17(6):2200-2211). Here, we analyzed the functional interaction between intracellular calcium channels and group I mGluRs to determine the contribution of these differentially distributed signaling proteins to group I mGluR agonist-induced intracellular Ca²⁺ signals in the first interneurons of the retina. Methods: Immunoreactivity for intracellular calcium channels in rod bipolar cells from rat and mouse retinas was detected using immunocytochemistry and specific antibodies. Intracellular Ca²⁺ concentrations were optically recorded in acutely isolated rod bipolar cells from rat and mouse retinas using receptor-specific pharmacological agonists and antagonists. Results: Whereas inositol (1,4,5)-trisphosphate receptor (IP3R) isoforms were differentially distributed, immunoreactivity for ryanodine receptor was not detected in rod bipolar cells. The distribution of IP3R isoforms was highly correlated with cytosolic Ca²⁺ transients that had been induced by activation of group I mGluRs leading to subsequent IP3 production. At the same time, the duration and kinetics of intracellular Ca²⁺ signals were also spatio-temporally correlated with biophysical properties of the differentially expressed IP3R isoforms in rod bipolar cells, IP3-sensitivity and activity dependence on the intracellular Ca²⁺ concentration. Conclusion: The differential distribution of intracellular Ca²⁺ release channels can be used by rod bipolar cells to convey Ca²⁺ signals that are distinct in their duration, amplitude and kinetics at the subcellular level, such as dendritic information processing, neurotransmitter release or activity-induced changes in protein expression. Supported by a German National Merit Scholarship Foundation scholarship (CM), a grant from The University of North Texas Health Science Center at Fort Worth Intramural Research Program (PK) and a Young Investigator Award from The National Alliance for Research on Schizophrenia and Depression (PK).

Keywords: calcium • ion channels • retina