| dc.creator | Mustafá, Emilio Román | |
| dc.creator | Cordisco Gonzalez, Santiago | |
| dc.creator | Raingo, Jesica | |
| dc.date | 2020-02 | |
| dc.date | 2022-02-11T13:59:10Z | |
| dc.date.accessioned | 2023-07-15T04:36:51Z | |
| dc.date.available | 2023-07-15T04:36:51Z | |
| dc.identifier | http://sedici.unlp.edu.ar/handle/10915/130925 | |
| dc.identifier | issn:1559-1182 | |
| dc.identifier | issn:0893-7648 | |
| dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/7470226 | |
| dc.description | The mechanisms by which ghrelin controls electrical activity in the hypothalamus are not fully understood. One unexplored target of ghrelin is Ca<sub>V</sub>3, responsible for transient calcium currents (T-currents) that control neuronal firing. We investigated the effect of ghrelin on Ca<sub>V</sub>3 subtypes and how this modulation impacts on neuronal activity. We performed whole-cell patch-clamp recordings in primary mouse hypothalamic cultures to explore the effect of ghrelin on T-currents. We also recorded calcium currents from transiently transfected tsA201 cells to study the sensitivity of each Ca<sub>V</sub>3 subtype to GHSR activation. Finally, we ran a computational model combining the well-known reduction of potassium current by ghrelin with the Ca<sub>V</sub>3 biophysical parameter modifications induced by ghrelin to predict the impact on neuronal electrical behavior. We found that ghrelin inhibits native NiCl₂ sensitive current currents in hypothalamic neurons. We determined that Ca<sub>V</sub>3.3 is the only Ca<sub>V</sub>3 subtype sensitive to ghrelin. The modulation of Ca<sub>V</sub>3.3 by ghrelin comprises a reduction in maximum conductance, a shift to hyperpolarized voltages of the I–V and steady-state inactivation curves, and an acceleration of activation and inactivation kinetics. Our model-based prediction indicates that the inhibition of Ca<sub>V</sub>3.3 would attenuate the stimulation of firing originating from the inhibition of potassium currents by ghrelin. In summary, we discovered a new target of ghrelin in neurons: the Ca<sub>V</sub>3.3. This mechanism would imply a negative feed-forward regulation of the neuronal activation exerted by ghrelin. Our work expands the knowledge of the wide range of actions of GHSR, a receptor potentially targeted by therapeutics for several diseases. | |
| dc.description | Facultad de Ciencias Exactas | |
| dc.description | Instituto Multidisciplinario de Biología Celular | |
| dc.format | application/pdf | |
| dc.format | 722-735 | |
| dc.language | en | |
| dc.rights | http://creativecommons.org/licenses/by-nc-sa/4.0/ | |
| dc.rights | Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) | |
| dc.subject | Ciencias Exactas | |
| dc.subject | Biología | |
| dc.subject | Ghrelin | |
| dc.subject | GHSR | |
| dc.subject | CaV3.3 | |
| dc.subject | Excitability | |
| dc.subject | Hypothalamus | |
| dc.title | Ghrelin Selectively Inhibits CaV3.3 Subtype of Low-Voltage-Gated Calcium Channels | |
| dc.type | Articulo | |
| dc.type | Articulo | |
