Papers In Press, published online ahead of print July 16, 2001
J. Biol. Chem, 10.1074/jbc.M105386200
Submitted on June 11, 2001
Revised on July 13, 2001
Accepted on July 13, 2001
Dependence of pituitary hormone secretion on the pattern of spontaneus voltage-gated calcium influx: cell-type specific action potential-secretion coupling
Fredrick Van Goor, Dragoslava Zivadinovic, Antonio J. Martinez-Fuentes, and Stanko S. Stojilkovic
Endocrinology and Reproduction Research Branch, National Institue of Child Health and Human Development, Bethesda, MD 20892-4510
Corresponding Author: stankos{at}helix.nih.gov
In excitable cells, voltage-gated calcium influx provides an effective mechanism for the activation of exocytosis. In this study, we demonstrate that although rat anterior pituitary lactotrophs, somatotrophs, and gonadotrophs exhibited spontaneous and extracellular calcium-dependent electrical activity, voltage-gated calcium influx triggered secretion only in lactotrophs and somatotrophs. The lack of action potential-driven secretion in gonadotrophs was not due to the proportion of spontaneously firing cells or spike frequency. Gonadotrophs exhibited comparable calcium signals during prolonged depolarization to those observed in somatotrophs and lactotrophs. The secretory vesicles in all three cell-types also had a similar sensitivity to voltage-gated calcium influx. However, the pattern of action potential calcium influx differed among three cell types. Spontaneous activity in gonadotrophs was characterized by high amplitude, sharp spikes that had a limited capacity to promote calcium influx, whereas lactotrophs and somatotrophs fired plateau-bursting action potentials, which generated high amplitude calcium signals. Furthermore, a shift in the pattern of firing from sharp spikes to plateau-like spikes in gonadotrophs triggered LH secretion. These results indicate that the cell-type specific action potential-secretion coupling in pituitary cells is determined by the capacity of their plasma membrane oscillator to generate threshold calcium signals.