Calcium influx mechanisms underlying calcium oscillations in rat hepatocytes.

Hepatology

Laboratory of Signal Transduction, National Institute of Environmental Health Sciences-NIH, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.

Published: October 2008

AI Article Synopsis

  • The study investigates the role of store-operated calcium (Ca(2+)) entry in rat hepatocytes, focusing on the proteins STIM1 and Orai1, which are crucial for this process.
  • Using pharmacological inhibitors and RNA interference techniques, researchers found that while blocking store-operated channels reduced calcium entry, it only slightly affected the frequency of hormone-induced calcium oscillations.
  • The conclusion highlights that store-operated Ca(2+) entry contributes to maintaining calcium oscillations, but additional mechanisms are also likely necessary for full agonist-induced responses.

Article Abstract

Unlabelled: The process of capacitative or store-operated Ca(2+) entry has been extensively investigated, and recently two major molecular players in this process have been described. Stromal interacting molecule (STIM) 1 acts as a sensor for the level of Ca(2+) stored in the endoplasmic reticulum, and Orai proteins constitute pore-forming subunits of the store-operated channels. Store-operated Ca(2+) entry is readily demonstrated with protocols that provide extensive Ca(2+) store depletion; however, the role of store-operated entry with modest and more physiological cell stimuli is less certain. Recent studies have addressed this question in cell lines; however, the role of store-operated entry during physiological activation of primary cells has not been extensively investigated, and there is little or no information on the roles of STIM and Orai proteins in primary cells. Also, the nature of the Ca(2+) influx mechanism with hormone activation of hepatocytes is controversial. Hepatocytes respond to physiological levels of glycogenolytic hormones with well-characterized intracellular Ca(2+) oscillations. In the current study, we have used both pharmacological tools and RNA interference (RNAi)-based techniques to investigate the role of store-operated channels in the maintenance of hormone-induced Ca(2+) oscillations in rat hepatocytes. Pharmacological inhibitors of store-operated channels blocked thapsigargin-induced Ca(2+) entry but only partially reduced the frequency of Ca(2+) oscillations. Similarly, RNAi knockdown of STIM1 or Orai1 substantially reduced thapsigargin-induced calcium entry, and more modestly diminished the frequency of vasopressin-induced oscillations.

Conclusion: Our findings establish that store-operated Ca(2+) entry plays a role in the maintenance of agonist-induced oscillations in primary rat hepatocytes but indicate that other agonist-induced entry mechanisms must be involved to a significant extent.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808042PMC
http://dx.doi.org/10.1002/hep.22461DOI Listing

Publication Analysis

Top Keywords

ca2+ entry
16
rat hepatocytes
12
store-operated ca2+
12
store-operated channels
12
role store-operated
12
ca2+ oscillations
12
ca2+
10
oscillations rat
8
store-operated
8
entry
8

Similar Publications

Mucociliary clearance (MCC) is a host defense mechanism of the respiratory system. Beating cilia plays a crucial role in the MCC process and ciliary beat frequency (CBF) is activated by several factors including elevations of the intracellular cAMP concentration ([cAMP]), intracellular Ca concentration ([Ca]), and intracellular pH (pH). In this study, we investigated whether an artichoke-extracted component cynaropicrin could be a beneficial compound for improving MCC.

View Article and Find Full Text PDF

Ca signaling events are essential for maintaining cardiovascular health, regulating critical functions in both endothelial and cardiac cells. SARS-CoV-2 infection impinges this delicate balance, leading to severe cardiovascular complications. SARS-CoV-2 binds to the ACE2 receptor on endothelial and cardiomyocyte surfaces, triggering abnormal increases in intracellular Ca levels that promote endothelial dysfunction, inflammation, and hypercoagulation.

View Article and Find Full Text PDF

Sjögren's disease (SjD) is an autoimmune disorder characterized by progressive salivary and lacrimal gland dysfunction, inflammation, and destruction, as well as extraglandular manifestations. SjD is associated with autoreactive B and T cells, but its pathophysiology remains incompletely understood. Abnormalities in regulatory T (T) cells occur in several autoimmune diseases, but their role in SjD is ambiguous.

View Article and Find Full Text PDF

The routing of blood flow throughout the brain vasculature is precisely controlled by mechanisms that serve to maintain a fine balance between local neuronal demands and vascular supply of nutrients. We recently identified two capillary endothelial cell (cEC)-based mechanisms that control cerebral blood flow in vivo: 1) electrical signaling, mediated by extracellular K-dependent activation of strong inward rectifying K (Kir2.1) channels, which are steeply activated by hyperpolarization and thus are capable of cell-to-cell propagation, and 2) calcium (Ca) signaling, which reflects release of Ca via the inositol 1,4,5-trisphosphate receptor (IPR)-a target of G-protein-coupled receptor signaling.

View Article and Find Full Text PDF

Store-Operated Ca Entry in Fibrosis and Tissue Remodeling.

Contact (Thousand Oaks)

December 2024

Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Fibrosis is a pathological condition characterized by excessive tissue deposition of extracellular matrix (ECM) components, leading to scarring and impaired function across multiple organ systems. This complex process is mediated by a dynamic interplay between cell types, including myofibroblasts, fibroblasts, immune cells, epithelial cells, and endothelial cells, each contributing distinctively through various signaling pathways. Critical to the regulatory mechanisms involved in fibrosis is store-operated calcium entry (SOCE), a calcium entry pathway into the cytosol active at the endoplasmic reticulum-plasma membrane contact sites and common to all cells.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: