Role of T-Type Calcium Channels in Neuroendocrine Differentiation
Neuroendocrine cells release their secretory products into the extracellular environment via a calcium-dependent pathway. These particular cells share common morphological and molecular features, such as the expression of specific biomarkers, neurite outg
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Role of T-Type Calcium Channels in Neuroendocrine Differentiation Marine Warnier, Florian Gackie`re, Morad Roudbaraki, and Pascal Mariot
Abstract
Neuroendocrine cells release their secretory products into the extracellular environment via a calcium-dependent pathway. These particular cells share common morphological and molecular features, such as the expression of specific biomarkers, neurite outgrowth and dense-core secretory granules. In order to elucidate the signalling pathways leading from undifferentiated to differentiated neuroendocrine cells, the role of voltage-dependent calcium channels and central actors in excitation–secretion coupling has been comprehensively investigated. T-type calcium channels, comprising of three different molecular isoforms, appear to be one of the important calcium channel families involved in the neuroendocrine differentiation process. They also may participate in the development of neuroendocrine tumours.
4.1
Introduction
Neuroendocrine (NE) cells produce and release (neuro)hormones, neuropeptides or monoamines in the extracellular milieu using a regulated pathway in response to a specific stimulus. The NE system includes specific organs, where cells are organized into secreting tissues (adrenals or pituitary, for instance), and a diffuse system, where endocrine cells are scattered in an apparently disorganized pattern among non-secretory cells. This diffuse NE system (DNES) was originally identified in organs, such as the lung and the gut. NE cells include both neuronM. Warnier (*) • F. Gackie`re • M. Roudbaraki • P. Mariot Laboratoire de Physiologie Cellulaire, Inserm U1003, Universite´ des Sciences et Technologies de Lille 1, 59650 Villeneuve d’Ascq, France Laboratory of Excellence, Ion Channels Science and Therapeutics, Universite´ des Sciences et Technologies de Lille 1, 59650 Villeneuve d’Ascq, France e-mail: [email protected] # Springer-Verlag Wien 2015 S.W. Schaffer, M. Li (eds.), T-type Calcium Channels in Basic and Clinical Science, DOI 10.1007/978-3-7091-1413-1_4
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like cells and endocrine cells that are all characterized by common morphological and molecular features, like the expression of specific markers such as neuropeptides, granins, neuritic extension or dense-core secretory granules. During their development, NE cells follow a differentiation pathway which, if faulty, may participate in the development of NE tumours (NET). It is therefore of particular importance to decipher the mechanisms involved in NE differentiation that are required to generate neurohormone-releasing cells.
4.2
Features of NE Cells and NE Differentiation
From a historical point of view, the concept of NE cells derives from the seminal works of Heidenhain, Kulchitsky, Masson and Hamperl in the late nineteenth century and the early twentieth century. Their studies demonstrated, from the ability of cells to be stained by silver salts (argentaffinity or argyrophily), the existence of dispersed hormone-secreting cells in non-endocrine tissues such a
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