Sensing and refilling calcium stores in an excitable cell

Yue Xian Li, Stanko S. Stojilković, Joel Keizer, John Rinzel

Research output: Contribution to journalArticle

Abstract

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 (I(crac)), 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 Ca2+- 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 n 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+] in the vicinity of the plasma membrane acts as a messenger for ER content via Ca2+-activated K+ channels and Ca2+ pumps in the plasma membrane. We conclude that, in excitable cells that do not express I(crac), [Ca2+](i) profiles provide a sensitive mechanism for regulating net calcium flux through the plasma membrane during both store depletion and refilling.

Original languageEnglish (US)
Pages (from-to)1080-1091
Number of pages12
JournalBiophysical journal
Volume72
Issue number3
DOIs
StatePublished - Mar 1997

ASJC Scopus subject areas

  • Biophysics

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