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Sensing and refilling calcium stores in an excitable cell
Y X Li1, S S Stojilković, J Keizer
1Mathematical Research Branch, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Biophysical Journal
|March 1, 1997
Summary
Inositol 1,4,5-trisphosphate (IP3)-induced calcium (Ca2+) release from the endoplasmic reticulum (ER) in gonadotrophs is sensed via voltage spikes, not Ca2+ release-activated Ca2+ current (ICRAC). This mechanism regulates Ca2+ entry in excitable cells lacking ICRAC.
Area of Science:
- Cellular and Molecular Physiology
- Endocrinology
- Calcium Signaling
Background:
- Inositol 1,4,5-trisphosphate (IP3) triggers Ca2+ release from the endoplasmic reticulum (ER), leading to ER depletion and increased Ca2+ entry.
- Capacitative Ca2+ entry is a key mechanism for replenishing ER Ca2+ stores, but its regulation in excitable cells lacking specific channels is not fully understood.
Purpose of the Study:
- To investigate the mechanism of ER Ca2+ content sensing and subsequent Ca2+ entry in gonadotrophs, a type of excitable endocrine cell.
- To develop and validate a computational model simulating agonist-induced Ca2+ dynamics in gonadotrophs.
Main Methods:
- Development of a comprehensive computational model integrating ER-mediated and plasma membrane potential-driven Ca2+ oscillations.
- Simulation of spatiotemporal Ca2+ signals in both the cytosol and ER lumen.
- Constraining model parameters with existing experimental data on Ca2+ signals and electrical activity.
Main Results:
- Demonstrated that ER Ca2+ sensing in gonadotrophs occurs via IP3-induced Ca2+ oscillations coupled to plasma membrane voltage spikes, independent of the Ca2+ release-activated Ca2+ current (ICRAC).
- Showed that capacitative Ca2+ entry is achieved through Ca2+-controlled Ca2+ entry.
- Model simulations agreed with experimental data and generated testable predictions regarding the role of localized cytosolic Ca2+ ([Ca2+]i) as a messenger for ER content.
Conclusions:
- In excitable cells lacking ICRAC, IP3-induced Ca2+ oscillations coupled to voltage spikes regulate Ca2+ entry, achieving capacitative Ca2+ entry.
- Cytosolic Ca2+ concentration ([Ca2+]i) near the plasma membrane acts as a messenger for ER Ca2+ content, influencing Ca2+ flux via plasma membrane channels and pumps.
- This mechanism provides a sensitive way to regulate net calcium flux during ER store depletion and refilling in specific cell types.