INVESTIGADORES
RAINGO Jesica
congresos y reuniones científicas
Título:
GHSR1a-constitutive activity inhibits presynaptic voltage gated calcium channels in cultured hypothalamic neurons
Autor/es:
LOPEZ SOTO JE; AGOSTI F; RODRÍGUEZ SS; CASTROGIOVANNI D; PERELLO M; 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:
Within
the hypothalamus, several peripheral signals have been shown to modulate neuronal
activity, including the orexigenic hormone ghrelin. Ghrelin effects are
mediated by Growth Hormone Secretagogue Receptor Type 1a (GHSR1a), the highest
constitutively activated G-protein coupled receptors known. We have already demonstrated
that GHSR1a-constitutive activity tonically inhibits presynaptic voltage gated
calcium channels (VGCC), CaV2.1 and CaV2.2, in a heterologous
system. Here, we aimed to determine if native levels of GHSR1a are enough to control
basal CaV2.1 and CaV2.2 currents in hypothalamic neurons. We performed whole-cell patch-clamp recordings in
embryonic hypothalamic neuronal cultures from GHSR-eGFP reporter mice. We found
that eGFP(+) neurons (expressing GHSR) have 50 % less of total native VGCC current
than eGFP(-) neurons (no expressing GHSR), whereas NaV currents were
not different between groups. Also, the application of exogenous ghrelin
inhibits 25 % of VGCC current only in GHSR-expressing neurons. Interestingly, we
observed a specific reduction of ω-Agatoxin IVA and ω-Conotoxin
GVIA (selective CaV2.1 and CaV2.2 blockers, respectively)
sensitive CaV currents in GHSR-expressing neurons, while conotoxin/agatoxin
insensitive CaV current remain unchanged. Our results demonstrated
that GHSR1a constitutive and ghrelin-evoked activity specifically inhibit
presynaptic VGCC in hypothalamic neurons