Differential Management of Ca ²⁺ Oscillations by Anterior Pituitary Cells: A Comparative Overview

Abstract

Most electrical and ionic properties of anterior pituitary cells are common to all pituitary cell types; only gonadotropes exhibit a few cell specific features. Under basal conditions, the majority of pituitary cells in vitro, irrespective of their cell type, display spontaneous action potentials and [Ca²⁺]_i transients that result from rhythmic Ca²⁺ entry through L-type Ca²⁺ channels. The main function of these action potentials is to maintain cells in a readily activable responsive state. We propose to call this state a ‘pacemaker mode’, since it persists in the absence of extrinsic stimulation. When challenged by hypothalamic releasing hormones, cells exhibit two distinct response patterns: amplification of pacemaker activity or shift to internal Ca²⁺ release mode. In the internal Ca²⁺ release mode, [Ca²⁺]_i oscillations are not initiated by entry of external Ca²⁺, but by release of Ca²⁺ from intracellular stores. In somatotropes and corticotropes, GHRH or CRH triggers the pacemaker mode in silent cells and amplifies it in spontaneously active cells. In contrast, in gonadotropes GnRH activates the internal Ca²⁺ release mode in silent cells and switches already active cells from the pacemaker to the internal Ca²⁺ release mode. Interestingly, homologous normal and tumoral cells display the same type of activity in vitro, in the absence or presence of hypothalamic hormones. Pacemaker and internal Ca²⁺ release modes are likely to serve different purposes. Pacemaker activity allows long-lasting sequences of [Ca²⁺]_i oscillations (and thus sustained periods of secretion) that stop under the influence of hypothalamic inhibitory peptides. In contrast, the time during which cells can maintain internal Ca²⁺ release mode depends upon the importance of intracellular Ca²⁺ stores. This mode is thus more adapted to trigger secretory peaks of large amplitude and short duration. On the basis of these observations, theoretical models of pituitary cell activity can be proposed.