INVESTIGADORES
RAINGO Jesica
congresos y reuniones científicas
Título:
Ghrelin receptor (GHSR1a) constitutive and ghrelin-evoked activities inhibit calcium channels through different signalling pathways.
Autor/es:
MARTÍNEZ DAMONTE V; LOPEZ SOTO JE; AGOSTI F; MUSTAFÁ ER; RODRÍGUEZ SS; RAINGO J
Lugar:
Huerta Grande
Reunión:
Congreso; XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2013
Institución organizadora:
Sociedad Argentina de Neurociencia
Resumen:
GHSR1a is a G-protein coupled receptor (GPCR) highly
expressed at the hypothalamus and by contrast to the most GPCRs, it exerts a
high constitutive activity. GHSR1a activity enhances neuronal excitability by acting
on several postsynaptic structures. This receptor is also present at axonal
terminals, but its physiological impact and the molecular mechanisms involved
in its presynaptic actions have not been addressed yet. Here, we postulate that
GHSR1a regulates presynaptic voltage-gated calcium channels (VGCC), the
structure that controls neurotransmitter release. We performed patch clamp
recordings and imaging analysis in HEK293t cells transiently transfected with
GHSR1a or GHSR1a-A204E (mutant lacking constitutive activity), and CaV2.1
or CaV2.2 and its auxiliary subunits. We found that GHSR1a
constitutive activity inhibits CaV2.1 and CaV2.2
currents. We also observed that GHSR1a constitutive activity acts through a Gαi/o
voltage independent mechanism. On the other hand, we observed that GHSR1a ghrelin-evoked
activity inhibits CaV2.1 and CaV2.2 by a different
pathway that depends on Gαq, Gβγ, and it is CaVβ subtype-dependent. Moreover, imaging analysis showed that GHSR1a constitutive activity impaired VGCC density
at the plasma membrane, likely by reducing its traffic. Our
results demonstrated that constitutive
and ghrelin-evoked GHSR1a activities inhibit presynaptic
calcium channels utilizing different pathways.