Ghrelin Selectively Inhibits CaV3.3 Subtype of Low-Voltage-Gated Calcium Channels

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 C...

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Detalles Bibliográficos
Autores principales: Mustafá, Emilio Román, Cordisco Gonzalez, Santiago, Raingo, Jesica
Formato: Articulo
Lenguaje:Inglés
Publicado: 2020
Materias:
Ciencias Exactas
Biología
Ghrelin
GHSR
CaV3.3
Excitability
Hypothalamus
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/130925
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-130925
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Biología
Ghrelin
GHSR
CaV3.3
Excitability
Hypothalamus
spellingShingle Ciencias Exactas
Biología
Ghrelin
GHSR
CaV3.3
Excitability
Hypothalamus
Mustafá, Emilio Román
Cordisco Gonzalez, Santiago
Raingo, Jesica
Ghrelin Selectively Inhibits CaV3.3 Subtype of Low-Voltage-Gated Calcium Channels
topic_facet Ciencias Exactas
Biología
Ghrelin
GHSR
CaV3.3
Excitability
Hypothalamus
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.
format Articulo
Articulo
author Mustafá, Emilio Román
Cordisco Gonzalez, Santiago
Raingo, Jesica
author_facet Mustafá, Emilio Román
Cordisco Gonzalez, Santiago
Raingo, Jesica
author_sort Mustafá, Emilio Román
title Ghrelin Selectively Inhibits CaV3.3 Subtype of Low-Voltage-Gated Calcium Channels
title_short Ghrelin Selectively Inhibits CaV3.3 Subtype of Low-Voltage-Gated Calcium Channels
title_full Ghrelin Selectively Inhibits CaV3.3 Subtype of Low-Voltage-Gated Calcium Channels
title_fullStr Ghrelin Selectively Inhibits CaV3.3 Subtype of Low-Voltage-Gated Calcium Channels
title_full_unstemmed Ghrelin Selectively Inhibits CaV3.3 Subtype of Low-Voltage-Gated Calcium Channels
title_sort ghrelin selectively inhibits cav3.3 subtype of low-voltage-gated calcium channels
publishDate 2020
url http://sedici.unlp.edu.ar/handle/10915/130925
work_keys_str_mv AT mustafaemilioroman ghrelinselectivelyinhibitscav33subtypeoflowvoltagegatedcalciumchannels
AT cordiscogonzalezsantiago ghrelinselectivelyinhibitscav33subtypeoflowvoltagegatedcalciumchannels
AT raingojesica ghrelinselectivelyinhibitscav33subtypeoflowvoltagegatedcalciumchannels
bdutipo_str Repositorios
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