Sensing and refilling calcium stores in an excitable cell

• Published in: Biophysical journal 1997-03, Vol.72 (3), p.1080-1091
• Main Authors: Li, Y.X., Stojilković, S.S., Keizer, J., Rinzel, J.
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Calcium Channels - physiology; Calcium-Transporting ATPases - metabolism; Cell Membrane - drug effects; Cell Membrane - physiology; Endoplasmic Reticulum - metabolism; Female; Gonadotropin-Releasing Hormone - pharmacology; In Vitro Techniques; Inositol 1,4,5-Trisphosphate - pharmacology; Inositol 1,4,5-Trisphosphate - physiology; Kinetics; Membrane Potentials; Models, Biological; Ovariectomy; Pituitary Gland, Anterior - drug effects; Pituitary Gland, Anterior - physiology; Rats; Sarcoplasmic Reticulum - metabolism
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/S0006-3495(97)78758-7

Inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ mobilization leads to depletion of the endoplasmic reticulum (ER) and an increase in Ca2+ entry. We show here for the gonadotroph, an excitable endocrine cell, that sensing of ER Ca2+ content can occur without the Ca2+ release-activated Ca2+ current (Icrac), but rather through the coupling of IP3-induced Ca2+ oscillations to plasma membrane voltage spikes that gate Ca2+ entry. Thus we demonstrate that capacitative Ca2+ entry is accomplished through Ca(2+)-controlled Ca2+ entry. We develop a comprehensive model, with parameter values constrained by available experimental data, to simulate the spatiotemporal behavior of agonist-induced Ca2+ signals in both the cytosol and ER lumen of gonadotrophs. The model combines two previously developed models, one for ER-mediated Ca2+ oscillations and another for plasma membrane potential-driven Ca2+ oscillations. Simulations show agreement with existing experimental records of store content, cytosolic Ca2+ concentration ([Ca2+]i), and electrical activity, and make a variety of new, experimentally testable predictions. In particular, computations with the model suggest that [Ca2+]i in the vicinity of the plasma membrane acts as a messenger for ER content via Ca(2+)-activated K+ channels and Ca2+ pumps in the plasma membrane. We conclude that, in excitable cells that do not express Icrac, [Ca2+]i profiles provide a sensitive mechanism for regulating net calcium flux through the plasma membrane during both store depletion and refilling.