Amplitude-Dependent Spike-Broadening and Enhanced Ca2+ Signaling in GnRH-Secreting Neurons

Model Status

This model runs in OpenCell and COR and the units are consistent throughout. Although it is a accurate reproduction of the published model it does not recreate the published results. Although the steady state values for some parameters are similar to published results, the model does not recreate the bursting seen in the paper and a stimulus protocl might need to be added.

Model Structure

ABSTRACT: In GnRH-secreting (GT1) neurons, activation of Ca(2+)-mobilizing receptors induces a sustained membrane depolarization that shifts the profile of the action potential (AP) waveform from sharp, high-amplitude to broad, low-amplitude spikes. Here we characterize this shift in the firing pattern and its impact on Ca(2+) influx experimentally by using prerecorded sharp and broad APs as the voltage-clamp command pulse. As a quantitative test of the experimental data, a mathematical model based on the membrane and ionic current properties of GT1 neurons was also used. Both experimental and modeling results indicated that inactivation of the tetrodotoxin-sensitive Na(+) channels by sustained depolarization accounted for a reduction in the amplitude of the spike upstroke. The ensuing decrease in tetraethylammonium-sensitive K(+) current activation slowed membrane repolarization, leading to AP broadening. This change in firing pattern increased the total L-type Ca(2+) current and facilitated AP-driven Ca(2+) entry. The leftward shift in the current-voltage relation of the L-type Ca(2+) channels expressed in GT1 cells allowed the depolarization-induced AP broadening to facilitate Ca(2+) entry despite a decrease in spike amplitude. Thus the gating properties of the L-type Ca(2+) channels expressed in GT1 neurons are suitable for promoting AP-driven Ca(2+) influx in receptor- and non-receptor-depolarized cells.

The original paper reference is cited below:

Amplitude-Dependent Spike-Broadening and Enhanced Ca²⁺ Signaling in GnRH-Secreting Neurons, Fredrick Van Goor, Andrew P. LeBeau, Lazar Z. Krsmanovic, Arthur Sherman, Kevin J. Catt and Stanko S. Stojikovic, 2000, Biophysical Journal, 79, 1310-1323. PubMed ID: 10968994