A Role of the Endoplasmic Reticulum in a Mathematical Model of Corticotroph Action Potentials
Paul R. Shorten, Andrew P. LeBeau, A. Bruce Robson, Alan E. McKinnon and David J.N. Wall
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Abstract
Pituitary corticotroph cells generate repetitive action potentials and associated Ca2+ transients in response to the agonist corticotropin releasing hormone (CRH). There is indirect evidence suggesting that the agonist, by way of complex intracellular mechanisms, modulates the voltage sensitivity of the L-type Ca2+ channels embedded in the plasma membrane. We have previously constructed a Hodgkin-Huxley type model of this process, which indicated that an increase in the L-type Ca2+ current is sufficient to generate repetitive action potentials [LeBeau et al. (1997). Biophysical Journal 73, 1263-1275].
In this paper we extend our model by including more realistic Ca2+ transport between cytosolic and endoplasmic compartments, and spatial variation in our description of the endoplasmic reticulum (ER) and cytosolic [Ca2+]. We have found firstly that this [Ca2+] spatial variation did not significantly affect the generation of action potentials, and secondly that gradual increase in the ER Ca2+ during repetitive action potential activity can ultimately feed back sufficient Ca2+ into the cytosol to eliminate action potentials. We discuss ways which cells might regulate their intracellular [Ca2+] dynamics to avoid such an effect.
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