Calcium oscillations in pituitary gonadotrophs

Comparison of experiment and theory

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

Research output: Contribution to journalArticle

Abstract

We have developed a mathematical model that describes several aspects of agonist-induced Ca2+ signaling in single pituitary gonadotrophs. Our model is based on fast activation of the inositol 1,4,5-trisphosphate (InsP3) receptor Ca2+ channels at low free cytosolic Ca2+ concentration ([Ca2+](i)) and slow inactivation at high [Ca2+](i). Previous work has shown that these gating properties, when combined with a Ca2+-ATPase, are sufficient to generate simulated Ca2+ oscillations. The Hodgkin-Huxley- like description we formulate here incorporates these different gating properties explicitly and renders their effects transparent and easy to modulate. We introduce regulatory mechanisms of channel opening which enable the model, both in the absence and in the presence of Ca2+ entry, to give responses to a wide range of agonist doses that are in good agreement with experimental findings, including subthreshold responses, superthreshold oscillations with frequency determined by [InsP3], and nonoscillatory 'biphasic' responses followed occasionally by small-amplitude oscillations. A particular added feature of our model, enhanced channel opening by reduced concentration of Ca2+ in the lumen of the endoplasmic reticulum, allows oscillations to continue during pool depletion. The model predicts that ionomycin and thapsigargin can induce oscillations with basal [InsP3] and zero Ca2+ entry, while Ca2+ injection cannot. Responses to specific pairings of sub- or superthreshold stimuli of agonist, ionomycin, and thapsigargin are also correctly predicted. Since this model encompasses a wide range of observed dynamic behaviors within a single framework, based on well-established mechanisms, its relevance should not be restricted to gonadotrophs.

Original languageEnglish (US)
Pages (from-to)58-62
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number1
DOIs
StatePublished - Jan 4 1994

Fingerprint

Gonadotrophs
Ionomycin
Thapsigargin
Calcium Signaling
Inositol 1,4,5-Trisphosphate Receptors
Calcium-Transporting ATPases
Endoplasmic Reticulum
Theoretical Models
Injections

Keywords

  • cytosolic Ca
  • inositol 1,4,5-trisphosphate receptor
  • luminal Ca
  • mathematical modeling
  • pool depletion

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Calcium oscillations in pituitary gonadotrophs : Comparison of experiment and theory. / Li, Yue Xian; Rinzel, John; Keizer, Joel; Stojilković, Stanko S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 1, 04.01.1994, p. 58-62.

Research output: Contribution to journalArticle

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