Modulation of the kinetics of inositol 1,4,5-trisphosphate-induced [Ca2+](i) oscillations by calcium entry in pituitary gonadotrophs

Abstract

Inositol 1,4,5-trisphosphate (InsP3) binds to its receptor channels and causes liberation of Ca2+ from intracellular stores, frequently in an oscillatory manner. In addition to InsP3, the activation and inactivation properties of these intracellular channels are controlled by Ca2+. We studied the influence of Ca2+ entry on the kinetics of InsP3-triggered oscillations in cytosolic calcium ([Ca2+](i)) in gonadotrophs stimulated with gonadotropin-releasing hormone, an agonist that activates InsP3 production. The natural expression of voltage-gated Ca2+ channels (VGCC) in these cells was employed to manipulate Ca2+ entry by voltage clamping the cells at different membrane potentials (V(m)). Under physiological conditions, the frequency of the GnRH-induced oscillations increased with time, while the amplitude decreased, until both reached stable values. However, in cells with V(m) held at -50 mV or lower, both parameters progressively decreased until the signal was abolished. These effects