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Melanocortin 4 receptor activation inhibits presynaptic N-type calcium channels in amygdaloid complex neurons

Francina Agosti1, Eduardo J López Soto, Agustina Cabral

  • 1Laboratory of Electrophysiology, Multidisciplinary Institute of Cell Biology (IMBICE), Argentine Research Council (CONICET) and Scientific Research Commission, Province of Buenos Aires (CIC-PBA), La Plata, Buenos Aires, Argentina.

The European Journal of Neuroscience
|June 20, 2014
PubMed

Insights

Melanocortin 4 receptor (MC4R) activation inhibits N-type calcium channels, impacting synaptic activity in the amygdala. This finding clarifies molecular mechanisms of MC4R signaling in regulating neuronal function.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Endocrinology

Background:

  • The melanocortin 4 receptor (MC4R) regulates food intake and energy balance, but its precise molecular mechanisms on neuronal activity are not fully understood.
  • MC4R signaling is known to influence the amygdala, a key brain region for appetite control.

Purpose of the Study:

  • To investigate whether MC4R activation modulates voltage-gated calcium channel activity and subsequent synaptic transmission.
  • To determine if these effects occur within the amygdala and contribute to MC4R-mediated functions.

Main Methods:

  • Utilized patch-clamp electrophysiology in HEK293 cells and cultured mouse amygdala neurons to assess calcium currents and synaptic activity.
  • Employed MC4R agonists (melanotan II, RO27-3225) and an N-type calcium channel blocker (ω conotoxin GVIA).
  • Measured cellular activity marker c-Fos in vivo in the amygdala.

Main Results:

  • MC4R activation by melanotan II specifically inhibited N-type calcium currents in both transfected cells and native amygdala neurons.
  • Melanotan II also reduced evoked inhibitory postsynaptic currents in amygdala neurons.
  • In vivo, MC4R agonist RO27-3225 increased c-Fos expression in the amygdala, with effects overlapping but distinct from the N-type channel blocker.

Conclusions:

  • MC4R activation specifically inhibits presynaptic N-type calcium channels.
  • This inhibition of N-type channels by MC4R is a key molecular mechanism underlying melanocortin signaling in the central amygdala.
  • The findings provide novel insights into the neurobiological regulation of appetite and energy homeostasis.
Keywords:
amygdalacalcium channelsmelanocortin receptormouse

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