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Biophys J, September 2000, p. 1310-1323, Vol. 79, No. 3

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

Fredrick Van Goor,* Andrew P. LeBeau,dagger Lazar Z. Krsmanovic,* Arthur Sherman,dagger Kevin J. Catt,* and Stanko S. Stojilkovic*

 *Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, and  dagger Mathematical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892 USA

In GnRH-secreting (GT1) neurons, activation of Ca2+-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 Ca2+ 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 Ca2+ current and facilitated AP-driven Ca2+ entry. The leftward shift in the current-voltage relation of the L-type Ca2+ channels expressed in GT1 cells allowed the depolarization-induced AP broadening to facilitate Ca2+ entry despite a decrease in spike amplitude. Thus the gating properties of the L-type Ca2+ channels expressed in GT1 neurons are suitable for promoting AP-driven Ca2+ influx in receptor- and non-receptor-depolarized cells.

Biophys J, September 2000, p. 1310-1323, Vol. 79, No. 3
© 2000 by the Biophysical Society   0006-3495/00/09/1310/14  $2.00


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