Amplitude-dependent spike-broadening and enhanced Ca(2+) signaling in GnRH-secreting neurons

Biophys J. 2000 Sep;79(3):1310-23. doi: 10.1016/S0006-3495(00)76384-3.

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.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / physiology*
  • Calcium Signaling / physiology*
  • Cell Line
  • Gonadotropin-Releasing Hormone / metabolism*
  • Kinetics
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects
  • Potassium Channels / physiology
  • Sodium Channels / drug effects
  • Sodium Channels / physiology
  • Tetraethylammonium / pharmacology
  • Tetrodotoxin / pharmacology

Substances

  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Potassium Channels
  • Sodium Channels
  • Gonadotropin-Releasing Hormone
  • Tetrodotoxin
  • Tetraethylammonium
  • Calcium