PEREZ MARIELA FERNANDA
Congresos y reuniones científicas
Título:
CALCINEURIN IS INVOLVED IN DOPAMINE D2-CLASS RECEPTOR (D2R)-MEDIATED INHIBITION OF HIGH-VOLTAGE ACTIVATED (HVA-) CA2+ CHANNEL ACTIVITY IN RAT NUCLEUS ACCUMBENS NEURONS
Autor/es:
GREVERS CM, PEREZ MF AND HUX-T
Lugar:
Atlanta, USA
Reunión:
Congreso; Society for Neuroscience; 2006
Institución organizadora:
Society for Neuroscience
Resumen:
The NAc is a critical forebrain region in the mesocorticolimbic dopamine (DA) system (the reward pathway) that regulates many aspects of drug addiction. The neuronal activity in the NAc is regulated by DA receptors. Although DA signaling has received considerable attention in the past decades, the mechanism underlying D2R modulation of the NAc activity is still ambiguous. Our previous studies have demonstrated that D2R stimulation enhance voltage-sensitive Na+ currents in NAc neurons via increasing intracellular Ca2+ release and stimulating Ca2+/calmodulin-activated calcineurin (also known as protein phosphatases 2B, PP2B), thereby leading to dephosphorilation of the Na+ channel. On the other hand, we have also found that D2R stimulation could reduce the duration of evoked HVA-Ca2+ plateau potentials in rat NAc neurons. These findings indicate that the D2R plays an important role in modulating intrinsic excitability of NAc neurons. However, although the inhibitory effects of D2Rs on Ca2+ channels are mimicked by blocking L-type Ca2+ channels, the cellular mechanism underlying D2R-modulated inhibition of Ca2+ plateau potentials remains unknown. In the present study we performed visualized whole-cell current-clamp recordings in brain slices to determine the signaling pathway(s) involved in the D2R-mediated inhibition of HVA-Ca2+ channel function in medium spiny NAc neurons located in the core region. Results from the present study indicate that cytosolic application of activated calcineurin (100 U/ml) not only mimicked but also occluded D2R-mediated inhibition in evoked Ca2+ plateau potentials. Inhibition of Ca2+ potentials induced by either direct D2R stimulation (quinpirole, 10 mM) or calcineurin was blocked by cyclosporin A, a selective calcineurin inhibitor. These findings indicate that the D2R-mediated inhibition of Ca2+ plateau potentials should be attributed to an enhanced dephosphorilation of L-type Ca2+ channels by calcineurin. Whether chronic cocaine exposure alters the D2R-mediated inhibition of Ca2+ potentials is currently under investigation.
