“…In humans, less than 10% of adrenal CCs exhibit spontaneous APs (Hernandez‐Vivanco et al . 2017) and in the spiking cells, although not investigated in detail, the AP pattern seems to be irregular, alternating between firing and silence periods, but without typical bursts. The data resulting from our analysis of APs engaged in a burst is consistent with previous results in dissociated mouse CCs (Vandael et al .…”
Section: Discussionmentioning
confidence: 95%
“…Although to a lesser extent, a spontaneous bursting pattern has been found in mouse CCs, both in cultured dissociated cells (Marcantoni et al 2010;Vandael et al 2015b) and in vivo in anaesthetized animals (Desarmenien et al 2013). In humans, less than 10% of adrenal CCs exhibit spontaneous APs (Hernandez-Vivanco et al 2017) and in the spiking cells, although not investigated in detail, the AP pattern seems to be irregular, alternating between firing and silence periods, but without typical bursts. The data resulting from our analysis of APs engaged in a burst is consistent with previous results in dissociated mouse CCs (Vandael et al 2015b), as such consecutive APs display a gradual reduction in the peak amplitude, AHP amplitude and ISI associated with an increase in the half-width duration and in intra-burst instantaneous firing frequency.…”
Section: Regular and Bursting Spontaneous Spiking Modes In Ccs: A Pec...mentioning
Key points
Mouse chromaffin cells in acute adrenal slices exhibit two distinct spiking patterns, a repetitive mode and a bursting mode.
A sodium background conductance operates at rest as demonstrated by the membrane hyperpolarization evoked by a low Na+‐containing extracellular saline.
This sodium background current is insensitive to TTX, is not blocked by Cs+ ions and displays a linear I‐V relationship at potentials close to chromaffin cell resting potential. Its properties are reminiscent of those of the sodium leak channel NALCN.
In the adrenal gland, Nalcn mRNA is selectively expressed in chromaffin cells.
The study fosters our understanding of how the spiking pattern of chromaffin cells is regulated and adds a sodium background conductance to the list of players involved in the stimulus‐secretion coupling of the adrenomedullary tissue.
Abstract
Chromaffin cells (CCs) are the master neuroendocrine units for the secretory function of the adrenal medulla and a finely‐tuned regulation of their electrical activity is required for appropriate catecholamine secretion in response to the organismal demand. Here, we aim at deciphering how the spiking pattern of mouse CCs is regulated by the ion conductances operating near the resting membrane potential (RMP). At RMP, mouse CCs display a composite firing pattern, alternating between active periods composed of action potentials spiking with a regular or a bursting mode, and silent periods. RMP is sensitive to changes in extracellular sodium concentration, and a low Na+‐containing saline hyperpolarizes the membrane, regardless of the discharge pattern. This RMP drive reflects the contribution of a depolarizing conductance, which is (i) not blocked by tetrodotoxin or caesium, (ii) displays a linear I‐V relationship between −110 and −40 mV, and (iii) is carried by cations with a conductance sequence gNa > gK > gCs. These biophysical attributes, together with the expression of the sodium‐leak channel Nalcn transcript in CCs, state credible the contribution of NALCN. This inaugural report opens new research routes in the field of CC stimulus‐secretion coupling, and extends the inventory of tissues in which NALCN is expressed to neuroendocrine glands.
“…In humans, less than 10% of adrenal CCs exhibit spontaneous APs (Hernandez‐Vivanco et al . 2017) and in the spiking cells, although not investigated in detail, the AP pattern seems to be irregular, alternating between firing and silence periods, but without typical bursts. The data resulting from our analysis of APs engaged in a burst is consistent with previous results in dissociated mouse CCs (Vandael et al .…”
Section: Discussionmentioning
confidence: 95%
“…Although to a lesser extent, a spontaneous bursting pattern has been found in mouse CCs, both in cultured dissociated cells (Marcantoni et al 2010;Vandael et al 2015b) and in vivo in anaesthetized animals (Desarmenien et al 2013). In humans, less than 10% of adrenal CCs exhibit spontaneous APs (Hernandez-Vivanco et al 2017) and in the spiking cells, although not investigated in detail, the AP pattern seems to be irregular, alternating between firing and silence periods, but without typical bursts. The data resulting from our analysis of APs engaged in a burst is consistent with previous results in dissociated mouse CCs (Vandael et al 2015b), as such consecutive APs display a gradual reduction in the peak amplitude, AHP amplitude and ISI associated with an increase in the half-width duration and in intra-burst instantaneous firing frequency.…”
Section: Regular and Bursting Spontaneous Spiking Modes In Ccs: A Pec...mentioning
Key points
Mouse chromaffin cells in acute adrenal slices exhibit two distinct spiking patterns, a repetitive mode and a bursting mode.
A sodium background conductance operates at rest as demonstrated by the membrane hyperpolarization evoked by a low Na+‐containing extracellular saline.
This sodium background current is insensitive to TTX, is not blocked by Cs+ ions and displays a linear I‐V relationship at potentials close to chromaffin cell resting potential. Its properties are reminiscent of those of the sodium leak channel NALCN.
In the adrenal gland, Nalcn mRNA is selectively expressed in chromaffin cells.
The study fosters our understanding of how the spiking pattern of chromaffin cells is regulated and adds a sodium background conductance to the list of players involved in the stimulus‐secretion coupling of the adrenomedullary tissue.
Abstract
Chromaffin cells (CCs) are the master neuroendocrine units for the secretory function of the adrenal medulla and a finely‐tuned regulation of their electrical activity is required for appropriate catecholamine secretion in response to the organismal demand. Here, we aim at deciphering how the spiking pattern of mouse CCs is regulated by the ion conductances operating near the resting membrane potential (RMP). At RMP, mouse CCs display a composite firing pattern, alternating between active periods composed of action potentials spiking with a regular or a bursting mode, and silent periods. RMP is sensitive to changes in extracellular sodium concentration, and a low Na+‐containing saline hyperpolarizes the membrane, regardless of the discharge pattern. This RMP drive reflects the contribution of a depolarizing conductance, which is (i) not blocked by tetrodotoxin or caesium, (ii) displays a linear I‐V relationship between −110 and −40 mV, and (iii) is carried by cations with a conductance sequence gNa > gK > gCs. These biophysical attributes, together with the expression of the sodium‐leak channel Nalcn transcript in CCs, state credible the contribution of NALCN. This inaugural report opens new research routes in the field of CC stimulus‐secretion coupling, and extends the inventory of tissues in which NALCN is expressed to neuroendocrine glands.
“…; Hernández‐Vivanco et al . ), but it has not been probed so far that these sAP can evoke the fusion of secretory vesicles with the plasma membrane, although catecholamine release has been determined (Vandael et al . ).…”
High catecolamine plasma levels because of sympathetic nervous system over-activity contribute to cirrhosis progression. The aim of this study was to investigate whether chromaffin cells of the adrenal gland might potentiate the deleterious effect exerted by this over-activity. Electrophysiological patch-clamp and amperometric experiments with carbon-fibre electrodes were conducted in single chromaffin cells of control and CCl 4induced cirrhotic rats. The spontaneous action potential firing frequency was increased in chromaffin cells of cirrhotic rats with respect to control rats. The exocytosis evoked by that firing was also increased. However, exocytosis elicited by ACh did not vary between control and cirrhotic rats. Exocytosis triggered by depolarizing pulses was also unchanged. Amperometric recordings confirmed the lack of increased catecholamine charge released in cirrhosis after ACh or depolarization stimuli. However, the amperometric spikes exhibited faster kinetics of release. The overall Ca 2+ entry through voltage-dependent Ca 2+ channels (VDCC), or in particular through Cav1 channels, did not vary between chromaffin cells of control and cirrhotic rats. The inhibition of VDCC by methionine-enkephaline or ATP was not either altered, but it was increased by adrenaline in cells of cirrhotic rats. When a cocktail composed by the three neurotransmitters was tested in order to approach a situation closer to the physiological condition, the inhibition of VDCC was similar between both types of cells. In summary, chromaffin cells of the adrenal gland might contribute to exacerbate the sympathetic nervous system over-activity in cirrhosis because of an increased exocytosis elicited by an enhanced spontaneous electrical activity.
“…The presence of L-type currents has been electrophysiologically characterized in bovine (4,11,12,17,18,20,37), rat (6,28,32,35,38,69,78), mouse (52,67,71,72), pig (58), cat (2,62), and human CCs (42,55).…”
Section: L-type Ca 2+ Channels In Chromaffin Cellsmentioning
confidence: 99%
“…Molecular evidence indicates that L-type currents in CCs is mediated by the expression of two subtypes of L-channels, a1C and a1D (13,46,47,55,66,92) and the most common view is that CCs express equal percentages of Cav1.2 and Cav1.3 L-type channels (68,72). However, on the basis of their affinities for DHPs, from RT-PCR, and from single channel recordings it is difficult to separate the contribution of these two channel types to the total L-type current (67,72,88).…”
Section: L-type Ca 2+ Channels In Chromaffin Cellsmentioning
The coexistence of different subtypes of voltage-dependent calcium channels (VDCC) within the same chromaffin cell (CC) and the marked interspecies variability in the proportion of VDCC subtypes that are present in the plasmalemma of the CCs raises the question on their roles in controlling different physiological functions. Particularly relevant seems to be the role of VDCCs in the regulation of the exocytotic neurotransmitter release process, and its tightly coupled membrane retrieval (endocytosis) process since both are Ca-dependent processes. This review is focused on the role of Ca influx through L-type VDCC in the regulation of these two processes. It is currently accepted that the different VDCC subtypes (i.e., T, L, N, P/Q, R) contribute to exocytosis proportionally to their density of expression and gating properties. However, the pattern of stimulation defines a preferential role of the different subtypes of VDCC on exocytosis and endocytosis. Thus, L-type channels seem to control catecholamine release induced by prolonged stimuli while fast exocytosis in response to short square depolarizing pulses or action potentials is mediated by Ca entering CCs through P/Q channels. The pattern of stimulation also influences the endocytotic process, and thus, electrophysiological data suggest the sustained Ca entry through slow-inactivating L-type channels could be responsible for the activation of fast endocytosis.
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