A Mathematical Model of Corticotroph action potentials
by
Paul Shorten
Universtity of Canterbury
Coauthors: Andrew P. LeBeau, A. Bruce Robson, Alan E. McKinnon, David J.N. Wall

Corticotropin releasing hormone (CRH) is one of the major regulatory hormones in the neuroendocrine response to stress. Secreted from CRH-neurons in the paraventricular nucleus of the hypothalamus, CRH travels through the hypothalmo-pituitary portal system to the anterior pituitary, where it stimulates the release of Adrenocorticotropic hormone (ACTH) and other biologically active hormones from the corticotroph cell population. The agonist CRH, by way of complex intracellular mechanisms, modulates the voltage sensitivity of the L-type Ca²⁺ channels embedded in the plasma membrane. The resulting potentiation of the L-type Ca²⁺ channels induces a membrane depolarization, that generates action potentials in quiescent corticotrophs, and enhances action potential frequency in spontaneously active corticotrophs. Associated with the action potentials are Ca²⁺ transients, predominately due to Ca²⁺ influx via L-type Ca²⁺ channels and efflux via plasma membrane Ca²⁺-ATPases. Ca²⁺ has been well established as an important intracellular trigger for hormone secretion. The spatio-temporal patterns in cytosolic Ca²⁺, generated by the subtle interplay between cellular Ca²⁺ sources and removal mechanisms, are believed to be an efficient way of transmitting the hormonal signal intracellularly. We have constructed a Hodgkin-Huxley type mathematical model of the major plasma membrane ionic currents and the associated intracellular Ca²⁺ dynamics identified in corticotrophs. The model has provided insight into the stimulus secretion coupled pathway.

Date received: May 22, 1998

Copyright © 1998 by the author(s). The author(s) of this document and the organizers of the conference have granted their consent to include this abstract in Atlas Conferences Inc. Document # cabd-22.