Ca2+ signaling and exocytosis in pituitary corticotropes

• Published in: Cell calcium (Edinburgh) 2012-03, Vol.51 (3), p.253-259
• Main Authors: Tse, Amy, Lee, Andy K, Tse, Frederick W
• Format: Article
• Language: English
• Subjects: Adrenocorticotropic hormone; Advanced Basic Science; Animals; Arachidonic acid; Arachidonic Acid - metabolism; Arginine vasopressin; Arginine Vasopressin - metabolism; Calcium - metabolism; Calcium Signaling; Corticotrophin-releasing hormone; Corticotrophs - physiology; Corticotropin-Releasing Hormone - metabolism; Endocytosis; Excitation Contraction Coupling; Exocytosis; Feedback, Physiological; Humans; Ion Transport; Mitochondria; Norepinephrine - metabolism; Readily releasable pool; Stress; TREK-1 channels
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2011.12.007

Abstract The secretion of adrenocorticotrophin (ACTH) from corticotropes is a key component in the endocrine response to stress. The resting potential of corticotropes is set by the basal activities of TWIK-related K+ (TREK)-1 channel. Corticotrophin-releasing hormone (CRH), the major ACTH secretagogue, closes the background TREK-1 channels via the cAMP-dependent pathway, resulting in depolarization and a sustained rise in cytosolic [Ca2+ ] ([Ca2+ ]i ). By contrast, arginine vasopressin and norepinephrine evoke Ca2+ release from the inositol trisphosphate (IP3 )-sensitive store, resulting in the activation of small conductance Ca2+ -activated K+ channels and hyperpolarization. Following [Ca2+ ]i rise, cytosolic Ca2+ is taken into the mitochondria via the uniporter. Mitochondrial inhibition slows the decay of the Ca2+ signal and enhances the depolarization-triggered exocytotic response. Both voltage-gated Ca2+ channel activation and intracellular Ca2+ release generate spatial Ca2+ gradients near the exocytic sites such that the local [Ca2+ ] is ∼3-fold higher than the average [Ca2+ ]i . The stimulation of mitochondrial metabolism during the agonist-induced Ca2+ signal and the robust endocytosis following stimulated exocytosis enable corticotropes to maintain sustained secretion during the diurnal ACTH surge. Arachidonic acid (AA) which is generated during CRH stimulation activates TREK-1 channels and causes hyperpolarization. Thus, corticotropes may regulate ACTH release via an autocrine feedback mechanism.