Abstract
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 calcium signals during prolonged depolarization comparable with signals 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 that generated high amplitude calcium signals. Furthermore, a shift in the pattern of firing from sharp spikes to plateau-like spikes in gonadotrophs triggered luteinizing hormone 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.
Highlights
In excitable cells, voltage-gated calcium influx provides an effective mechanism for the activation of exocytosis
These results demonstrate that basal growth hormone (GH) and PRL secretion from perifused anterior pituitary cells is Ϸ 25- and 40-fold higher, respectively, than luteinizing hormone (LH) secretion
We examined the ionic mechanisms underlying the different patterns of basal hormone secretion from anterior pituitary somatotrophs, lactotrophs, and gonadotrophs
Summary
A shift in the pattern of firing from sharp spikes to plateau-like spikes in gonadotrophs triggered luteinizing hormone 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. The differences in the patterns of basal hormone secretion may be due to differences in the ability of voltage-gated Ca2ϩ influx (VGCI) to increase intracellular calcium concentration ([Ca2ϩ]i) and stimulate secretion in spontaneously active cells. Our results indicate specific profiles of the AP wave forms in three cell types, and their ability to drive Ca2ϩ influx through voltage-gated Ca2ϩ channels (VGCCs) accounts for the cell type-specific patterns of basal hormone secretion. Gonadotrophs fired sharp, high amplitude APs with a limited capacity to drive Ca2ϩ influx, whereas lactotrophs and somatotrophs exhibited plateau-bursting activity that had a high capacity to drive Ca2ϩ entry
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