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Communication Dans Un Congrès Année : 2017

Stress-mediated remodeling of gap junctional communication in the adrenal medullary tissue

Résumé

In mammals, catecholamine secretion from adrenal chromaffin cells represents an ubiquitous mechanism helping the organism to cope with stressful situations. Once delivered into the blood circulation, epinephrine and norepinephrine exert multiple actions, in particular on the cardiovascular system, leading to appropriate adjustments of blood pressure and cardiac rhythm, and on the energy metabolism, enabling the organism to cope with a threat for its survival. While an instantaneous secretion of catecholamines is beneficial to face an acute stress episode, repeated or prolonged stressful situations resulting in sustained blood catecholamine increases are detrimental for the organism and can initiate many diseases. Catecholamine secretion from adrenal chromaffin cells relies on both a neurogenic command arising from the splanchnic nerve terminals synapsing onto chromaffin cells and a local gap junction-mediated intercellular communication between chromaffin cells (1). This symposium presentation will be focused on the remodeling of the gap junctional coupling occurring in response to a physiological stress (5 day-cold exposure, male Wistar rats) or a stress-related pathology (arterial hypertension using the animal model of spontaneously hypertensive rats (SHRs)). In acute adrenal slices of cold stressed rats, the gap junction-dependent communication between chromaffin cells is enhanced. This correlates with the appearance of a robust electrical coupling, allowing action potentials to propagate between coupled cells (2). Accordingly, synchronized spontaneous and nicotine-evoked [Ca2+]i rises between chromaffin cells are more frequently observed in stressed animals. These findings are associated with an increased expression of Cx36 and Cx43, the two main connexins expressed in rat chromaffin cells. A stress-triggered upregulation of gap junctional coupling is similarly observed in mice. Indeed, Cx36 expression is enhanced in chromaffin cells of cold stressed mice, and as shown by in vivo experiments performed in anaesthetized mice, the uncoupling agent carbenoxolone more robustly reduces catecholamine secretion in stressed mice compared to controls (3). Collectively, these results demonstrate that in response to a physiological stress, gap junction-mediated intercellular communication between chromaffin cells positively contribute to the adrenal excitation-secretion coupling and ensuing catecholamine secretion. Strengthening the decisive role of connexin-dependent signaling in regulating stimulus-secretion coupling of the adrenal medullary tissue is our recent findings obtained in the pathological context of arterial hypertension, a pathology in which a sustained plasma catecholamine elevation can contribute to. Gap junction-mediated chromaffin cell communication was investigated in SHRs and compared to age-matched normotensive Wistar Kyoto (WKY) rats. In SHR acute adrenal slices, LY diffusion between chromaffin cells is significantly reduced, resulting in less that 20% of dye-coupled cells. This parallels a decrease in both Cx43 mRNA and protein, but not in Cx36. Although not yet completed by functional experiments (monitoring of junctional currents between chromaffin cell pairs), these results argue for a reduced gap junctional communication between chromaffin cells in chronically hypertensive rats. As such, depending on the physiological or pathological context, the adrenal medullary tissue dualistically and accurately adapts the competence of the gap junctional coupling between chromaffin cells. This reinforces gap junction signaling as a substantial component for neuroendocrine function in the adrenal medulla, as it may represent an additional lever regulating hormone release.
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Dates et versions

hal-02735203 , version 1 (02-06-2020)

Identifiants

  • HAL Id : hal-02735203 , version 1
  • PRODINRA : 491742

Citer

Michel G Desarménien, Vincent Paille, Bertrand Toutain, Christian Legros, Nathalie C Guérineau. Stress-mediated remodeling of gap junctional communication in the adrenal medullary tissue. 6th conference of the Mediterranean Neuroscience Society, 2017, St. julian's, Malta. ⟨hal-02735203⟩
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