Gap junction-mediated intercellular communication in the adrenal medulla: An additional ingredient of stimulus–secretion coupling regulation

Abstract

The traditional understanding of stimulus-secretion coupling in adrenal neuroendocrine chromaffin cells states that catecholamines are released upon trans-synaptic sympathetic stimulation mediated by acetylcholine released from the splanchnic nerve terminals. Although this statement remains largely true, it deserves to be tempered. In addition to its neurogenic control, catecholamine secretion also depends on a local gap junction-mediated communication between chromaffin cells. We review here the insights gained since the first description of gap junctions in the adrenal medullary tissue. Adrenal stimulus-secretion coupling now appears far more intricate than was previously envisioned and its deciphering represents a challenge for neurobiologists engaged in the study of the regulation of neuroendocrine secretion. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.

Gap junction signalling is a stress-regulated component of adrenal neuroendocrine stimulus-secretion coupling in vivo

“…However, compelling evidence obtained in acute adrenal slices indicates that neurosecretory mechanisms are more intricate than previously envisioned. Indeed, catecholamine release appears to be dualistically controlled by an incoming initial command assisted by local modulation 6,7 , supporting the hypothesis of an amplifying system occurring at the chromaffin cell level 8 . The command triggering catecholamine secretion comes from the sympathetic nervous system synapsing onto chromaffin cells.…”

“…The underlying default likely occurs presynaptically, as suggested by the substantial reduction of both NF and VAChT immunolabelling. Although connexin-dependent signalling and chemical synaptic neurotransmission interact with each other in various neuronal tissues 58 , including in the adrenal medulla 6,7,59 , our finding reveals an unanticipated role for Cx36 at the splanchnic nerve-chromaffin cell synapse. During postnatal development, downregulation of adrenal gap junctional communication parallels the acquisition of the neurogenic control of catecholamine secretion 4,12 .…”

“…Although ketamine does not modify basal catecholamine secretion 45 , a direct measurement of plasma catecholamines, in a freely moving mouse submitted or not to various stress paradigms, will be necessary to definitely answer this question. Although a direct cell-cell communication through gap junctions has been described in many endocrine/neuroendocrine tissues [46][47][48][49] , including the adrenal medulla 6,7,11 , its contribution to hormone secretion in vivo has been unambiguously established so far only for insulin 50,51 and renin 49,52 . Very recent studies performed in the anterior pituitary 53,54 strongly support a crucial role for gap junctions in endocrine tissue output, suggesting that the plasticity of gap junction-coupled endocrine cell network is a key element underlying functional adaptation of hormone release at the population level.…”

CaV1.3-Driven SK Channel Activation Regulates Pacemaking and Spike Frequency Adaptation in Mouse Chromaffin Cells

“…Indeed, the catecholamine release induced by trains of electrical stimulations (0.1-30 Hz) reaches peak values between 3 and 10 Hz and then declines in rat and cat chromaffin cells (Wakade, 1981;Alamo et al, 1991;Montiel et al, 1995). The second implication is that, similar to certain neuronal assemblies (Ladenbauer et al, 2012), the phasic response related to adaptation currents (e.g., SK) described here may help firing synchronization in the adrenal medulla where chromaffin cells are electrically coupled (Colomer et al, 2012). Synchronization followed by adaptation to low-firing frequencies in extended areas of the adrenal medulla may optimize the release of cat-echolamines during intense prolonged stressful stimulation, preventing excessive accumulation of undesired levels of circulating catecholamines.…”

Pituitary adenylate cyclase-activating peptide enhances electrical coupling in the mouse adrenal medulla

“…Connexin channels bridge the cytoplasm of two cells and allow the diffusion of ions or second messengers. The prevalence and connexin composition of gap junction coupling in the adrenal medulla are dependent on age (30,32), species (10,20), gender (9,33), stress state (12), or splanchnic innervation (30,32). The role of gap junctions in normal adrenal physiology has been studied and implicated in modulation of adrenal excitation.…”