An Integrated Model of Electrical Spiking, Bursting, and Calcium Oscillations in GnRH Neurons

• Published in: Biophysical journal 2009-06, Vol.96 (11), p.4514-4524
• Main Authors: Fletcher, Patrick A., Li, Yue-Xian
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Algorithms; Apamin - administration & dosage; Biophysical Theory and Modeling; Calcium; Calcium - metabolism; Cells; Colforsin - administration & dosage; Cyclic AMP - administration & dosage; Enzyme Inhibitors - administration & dosage; Gonadotropin-Releasing Hormone - metabolism; Ions; Membrane Potentials - drug effects; Membrane Potentials - physiology; Membranes; Models, Neurological; Neurons; Neurons - drug effects; Neurons - physiology; Neurotoxins - administration & dosage; Sodium - metabolism; Studies; Thapsigargin - administration & dosage
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/j.bpj.2009.03.037

The plasma membrane electrical activities of neurons that secrete gonadotropin-releasing hormone (GnRH) have been studied extensively. A couple of mathematical models have been developed previously to explain different aspects of these activities. The goal of this article is to develop a single model that accounts for the previously modeled experimental results and some more recent results that have not been accounted for. The latter includes two types of membrane potential bursting mechanisms and their associated cytosolic calcium oscillations. One bursting mechanism has not been reported in experiments and is thus regarded as a model prediction. Although the model is mainly based on data collected in immortalized GnRH cell lines, it is capable of explaining some properties of GnRH neurons observed in several other preparations including mature GnRH neurons in hypothalamic slices. We present a spatial model that incorporates a detailed description of calcium dynamics in a three-dimensional cell body with the ion channels evenly distributed on the cell surface. A phenomenological reduction of the spatial model into a simplified form is also presented. The simplified model will facilitate the study of the roles of plasma membrane electrical activities in the pulsatile release of GnRH.