scholarly journals Inositol 1,4,5-Trisphosphate Receptor Subtype-Specific Regulation of Calcium Oscillations

2011 ◽  
Vol 36 (7) ◽  
pp. 1175-1185 ◽  
Author(s):  
Songbai Zhang ◽  
Nicolas Fritz ◽  
Cristian Ibarra ◽  
Per Uhlén
Keyword(s):  
Calcium Oscillations ◽  
Receptor Subtype ◽  
Inositol 1,4,5 Trisphosphate ◽  
Specific Regulation ◽  
Trisphosphate Receptor

Effect of halothane on intracellular calcium oscillations in porcine tracheal smooth muscle cells

1999 ◽  
Vol 276 (1) ◽  
pp. L81-L89 ◽  
Author(s):  
Christina M. Pabelick ◽  
Y. S. Prakash ◽  
Mathur S. Kannan ◽  
Keith A. Jones ◽  
David O. Warner ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Ryanodine Receptor ◽  
Muscle Cells ◽  
Calcium Oscillations ◽  
Tracheal Smooth Muscle ◽  
Permeabilized Cells ◽  
Inositol 1,4,5 Trisphosphate ◽  
Intracellular Ca ◽  
Trisphosphate Receptor

The effect of halothane on intracellular Ca2+ concentration ([Ca2+]i) regulation in porcine tracheal smooth muscle cells was examined with real-time confocal microscopy. Both 1 and 2 minimum alveolar concentration (MAC) halothane increased basal [Ca2+]iwhen Ca2+ influx and efflux were blocked, suggesting increased sarcoplasmic reticulum (SR) Ca2+ leak and/or decreased reuptake. In β-escin-permeabilized cells, heparin inhibition of inositol 1,4,5-trisphosphate-receptor channels blunted the halothane-induced increase in [Ca2+]i. Both 1 and 2 MAC halothane decreased the frequency and amplitude of ACh-induced [Ca2+]ioscillations (which represent SR Ca2+ release through ryanodine-receptor channels), abolishing oscillations in ∼20% of tracheal smooth muscle cells at 2 MAC. When Ca2+ influx and efflux were blocked, halothane increased the baseline and decreased the frequency and amplitude of [Ca2+]ioscillations, inhibiting oscillations in ∼70% of cells at 2 MAC. The fall time of [Ca2+]ioscillations and the rate of fall of the [Ca2+]iresponse to caffeine were both increased by halothane. These results suggest that halothane abolishes agonist-induced [Ca2+]ioscillations by 1) depleting SR Ca2+ via increased Ca2+ leak through inositol 1,4,5-trisphosphate-receptor channels, 2) decreasing Ca2+ release through ryanodine-receptor channels, and 3) inhibiting reuptake.

scholarly journals Cell Signaling Microdomain with Na,K-ATPase and Inositol 1,4,5-Trisphosphate Receptor Generates Calcium Oscillations

2003 ◽  
Vol 278 (50) ◽  
pp. 50355-50361 ◽  
Author(s):  
Ayako Miyakawa-Naito ◽  
Per Uhlén ◽  
Mark Lal ◽  
Oleg Aizman ◽  
Katsuhiko Mikoshiba ◽  
...  
Keyword(s):  
Cell Signaling ◽  
Calcium Oscillations ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

scholarly journals Isoform-specific Regulation of the Inositol 1,4,5-Trisphosphate Receptor by O-Linked Glycosylation

2011 ◽  
Vol 286 (18) ◽  
pp. 15688-15697 ◽  
Author(s):  
Patricia Bimboese ◽  
Craig J. Gibson ◽  
Stefan Schmidt ◽  
Wanqing Xiang ◽  
Barbara E. Ehrlich
Keyword(s):  
Intracellular Calcium ◽  
Cell Line ◽  
Calcium Release ◽  
Single Channel ◽  
Open Probability ◽  
Functional Changes ◽  
Inositol 1,4,5 Trisphosphate ◽  
Cholangiocarcinoma Cell ◽  
Specific Regulation ◽  
Trisphosphate Receptor

The inositol 1,4,5-trisphosphate receptor (InsP3R), an intracellular calcium channel, has three isoforms with >65% sequence homology, yet the isoforms differ in their function and regulation by post-translational modifications. We showed previously that InsP3R-1 is functionally modified by O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) (Rengifo, J., Gibson, C. J., Winkler, E., Collin, T., and Ehrlich, B. E. (2007) J. Neurosci. 27, 13813–13821). We now report the effect of O-GlcNAcylation on InsP3R-2 and InsP3R-3. Analysis of AR4-2J cells, a rat pancreatoma cell line expressing predominantly InsP3R-2, showed no detectable O-GlcNAcylation of InsP3R-2 and no significant functional changes despite the presence of the enzymes for addition (O-β-N-acetylglucosaminyltransferase) and removal (O-β-N-acetylglucosaminidase) of the monosaccharide. In contrast, InsP3R-3 in Mz-ChA-1 cells, a human cholangiocarcinoma cell line expressing predominantly InsP3R-3, was functionally modified by O-GlcNAcylation. Interestingly, the functional impact of O-GlcNAcylation on the InsP3R-3 channel was opposite the effect measured with InsP3R-1. Addition of O-GlcNAc by O-β-N-acetylglucosaminyltransferase increased InsP3R-3 single channel open probability. Incubation of Mz-ChA-1 cells in hyperglycemic medium caused an increase in the InsP3-dependent calcium release from the endoplasmic reticulum. The dynamic and inducible nature of O-GlcNAcylation and the InsP3R isoform specificity suggest that this form of modification of InsP3R and subsequent changes in intracellular calcium transients are important in physiological and pathophysiological processes.

scholarly journals Disrupted Ca2+ homeostasis and immunodeficiency in patients with functional Inositol 1,4,5-trisphosphate receptor subtype 3 defects

2021 ◽  
Author(s):  
Julika Neumann ◽  
Erika van Nieuwenhove ◽  
Lara E Terry ◽  
Frederik Staels ◽  
Taylor R Knebel ◽  
...  
Keyword(s):  
Lymphocyte Activation ◽  
Cell Receptor ◽  
Receptor Subtype ◽  
Compound Heterozygous ◽  
Inborn Errors ◽  
Hematopoietic Stem ◽  
Inositol 1,4,5 Trisphosphate ◽  
Severe Immunodeficiency ◽  
Compound Heterozygous Variants ◽  
Trisphosphate Receptor

Calcium signaling is essential for lymphocyte activation, with genetic disruptions resulting in severe immunodeficiency. The inositol 1,4,5-trisphosphate receptor (IP3R), formed from homo- or hetero-tetramers of the IP3R isoforms 1-3, amplifies lymphocyte signaling by releasing Ca2+ from ER stores into the cytosol following antigen-stimulation. While knockout of all 3 IP3R isoforms results in immunodeficiency in mice, the seeming redundancy of subunits was thought to explain the absence of IP3R mutation as a cause of human immunodeficiency. Here, we identify compound heterozygous variants in ITPR3 in two unrelated Caucasian patients presenting with combined immunodeficiency, in one case requiring hematopoietic stem cell transplantation. We observed disrupted Calcium homeostasis in patient-derived fibroblasts and immune cells, with abnormal proliferation and activation responses following B and T cell receptor stimulation. Reconstitution of IP3R knockout cell lines identified the variants as functional hypomorphs with reduced discrimination between homeostatic and induced states, validating a link between genotype and phenotype. These results demonstrate a functional linkage between defective ER Ca2+ channels and immunodeficiency, and identify IP3Rs as diagnostic targets for patients with specific inborn errors of immunity.

Sign in / Sign up

Export Citation Format

Share Document