Modeling plasma membrane and endoplasmic reticulum excitability in pituitary cells

The response of gonadotrophs to secretagogues involves dose-dependent, complex dynamic patterns of electrical activity and inositol 1, 4, 5- trisphosphate (Ins P₃)-induced Ca²⁺ mobilization, including pulsatility and oscillations on multiple time scales from milliseconds to minutes. Detailed in vitro experiments have enabled the identification of key mechanisms that underlie the plasma membrane (PM) electrical excitability and endoplasmic reticulum (ER) calcium excitability. We summarize these findings and review computer simulations of a biophysical model that resynthesizes and couples these components and that reproduces quantitatively the observed time courses and dose-response characteristics, as well as effects of various pharmacological manipulations. The theory suggests that cytosolic calcium is the primary messenger in coordinating the PM and ER regenerative behaviors during ER depletion and refilling.