Andrew P. Le Beau
Mathematical Research Branch
NIDDK and Endocrinology and Reproductive Research Branch
National Institutes of Health
Bethesda, MD 20892
Joint work with F. Van Goor, S.S. Stojilkovic and A. Sherman.
GT1 neurons, a gonadotropin-releasing hormone (GnRH)-secreting cell line, fire spontaneous action potentials (APs) in culture. Ionic currents underlying AP firing include a tetrodotoxin-sensitive Na current, L- and T-type Ca conductances and multiple K currents. Other conductances, not important for actual AP firing, may instead influence membrane excitability and thus AP firing frequency. GnRH secretion in GT1 cells, as is typical in other neurosecretory cells, is dependent on the intracellular Ca concentration. This in turn is dependent on the frequency of AP firing which is slow (in the range 0.5 -- 2 Hz) at rest, but which is enhanced following agonist stimulation.
To complement experimental investigations, we are investigating the control of AP firing frequency by construction of a mathematical model of GT1 cell electrophysiology. The model will be used 1) to determine the role of each major ionic conductance in the control of AP frequency and 2) to investigate the properties of smaller (i.e. non-spike contributing) conductances which may influence firing frequency.
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