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. 2024 Jan 17;46(1):808-820.
doi: 10.3390/cimb46010052.

The Role of Nicotinic Receptors on Ca2+ Signaling in Bovine Chromaffin Cells

Amparo Gil  1 , Virginia González-Vélez  2 , Luis Miguel Gutiérrez  3 , José Villanueva  3
Affiliations

The Role of Nicotinic Receptors on Ca2+ Signaling in Bovine Chromaffin Cells

Amparo Gil et al. Curr Issues Mol Biol. .

Abstract

Chromaffin cells have been used as a physiological model to understand neurosecretion in mammals for many years. Nicotinic receptors located in the cells' membrane are stimulated by acetylcholine, and they participate in the exocytosis of chromaffin granules, releasing catecholamines in response to stress. In this work, we discuss how the participation of nicotinic receptors and the localization of active zones in the borders of the cytoskeleton can generate local calcium signals leading to secretion. We use a computational model of a cytoskeleton cage to simulate Ca2+ levels in response to voltage and acetylcholine pulses. We find that nicotinic receptors are able to enhance the differences between local and average calcium values, as well as the heterogeneous distributions around the active zones, producing a non-linear, highly localized Ca2+ entry that, although consisting of a few ions, is able to improve secretion responses in chromaffin cells. Our findings emphasize the intricate interplay among nicotinic receptors, the cytoskeleton, and active zones within chromaffin cells as an example of Ca2+-dependent neurosecretion in mammals.

Keywords: Ca2+; acetylcholine nicotinic receptors; chromaffin cells; exocytosis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Geometrical model. (A) First slice of the cylinder shown in (B) where VDCC, ACh receptors, and vesicles are located. This draw exemplifies the Border configuration tested in the work where all mechanisms are located next to the perimeter of the slice. (B) Cylinder representing a prototypical cytoskeleton cage with a radius (r) of 0.3 μm and a height (h) of 1 μm. (C) State model of the nicotinic receptors.
Figure 2
Figure 2
Plasmalemmal α3-GFP (green) and LifeAct-RFP (red) co-expression in cultured chromaffin cells. Panel (A) shows images corresponding to a confocal microscopy plane obtained from the central zone of the cell. Panel (B) corresponds to a polar upper section (TOP) image of the cell. In both planes, the left image corresponds to the α3-EGFP channel, the central image to the LifeAct-RFP channel, and the right image to both merged channels. Panel (C) shows the XY distance distribution (nm) between the α3-EGFP and LifeAct-RFP centroids obtained from cortical plane images at the top or bottom of the cells (n = 86, 9 cells from 2 distinct cultures). Bar: 1 μm.
Figure 3
Figure 3
Cortical distribution of α3-EGFP and SNAP25-DsRed 48 h co-expression. Panel (A) shows the α3-EGFP channel alone. Panel (B) shows a merged image of α3-EGFP (green) and SNAP25-Dsred (red) co-expression. Panel (C) shows the average distance distribution between the centroids of each α3-EGFP patch and the centroids of the nearest SNAP-25-DsRed (see text). (n = 95, 12 cells, from 2 distinct cultures.) All records were obtained using sequential laser excitation and acquisition. Bar: 1 μm.
Figure 4
Figure 4
Differences in calcium distributions and intensities when VDCCs are located in different zones of the cytoskeletal cage. (A): The 50 ms depolarizing pulse from −50 mv to −20 mV used to stimulate VDCC in the model. (B): Dynamics of average calcium obtained when VDCCs are located on the border (left panel) or in the center (right panel) of the cage model. (C): Calcium maps showing the spatial distribution of calcium ions, for the two locations, when the voltage pulse had finished (after 50 ms).
Figure 5
Figure 5
Average calcium concentrations in response to the simulated protocol shown in (A). Values obtained between 0–30 nm (left panels in (B,C)) and 60–90 nm (right panels in (B,C)) from the cell membrane. (B): Results obtained for the Border configuration. (C): Results obtained for the Center configuration.
Figure 6
Figure 6
Calcium maps showing local calcium concentrations up to 30 nm from the cell membrane, at two different times after starting the simulated protocol shown in Figure 4A. (A): Border configuration. (B): Center configuration.
Figure 7
Figure 7
Simulated accumulated secretion in response to a 50 ms voltage pulse alone (first and third bars), or with a previous pulse of ACh (second and fourth bars). Results obtained with the Border and Center configurations of the model.
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