Exploring the functional interactions between the D2-receptors and L-type calcium channels in the control of striatal dopamine release

Dopamine (DA) release by nigrostriatal DA neurons is critical for selection and learning of movement and motivation. Parkinsonâs disease (PD) is characterized by the loss of these neurons and the resultant decrease in DA. Release of DA is governed by presynaptic voltage gated calcium channels (VGCCs). The entry of calcium to these DA neurons through the L-type VGCC has been hypothesised to be a possible cause of susceptibility to degeneration. Therefore, understanding the modulation of L-type VGCCs could be important to understanding their role in PD. DA release can be strongly regulated by D2 autoreceptors (D2Rs) which act through Gαi/o-PCR coupled mechanisms. They decrease transmitter release via a βγ-mediated inhibition of VGCCs. To investigate the functional interaction between D2 autoreceptors and L-type calcium channels in modulating release of dopamine, I use fast scan cyclic voltammetry to detect DA release in mouse acute striatal sections at carbon fibre microelectrodes with sub-second temporal resolution. In the CPu, D2 receptors do not modulate L-type VGCCs; there is a lack of functional interaction between D2Rs and L-type VGCCs in controlling striatal DA release. The addition of an L-channel blocker in the presence of a D2 receptor antagonist did not reduce DA release in a manner significantly different from the addition of the L-channel blocker in the absence of the D2 antagonist. This lack of effect was maintained even in the presence of cocaine which increases extracellular DA and therefore the activation of D2 receptors. In the NAc, D2 autoreceptors inhibit the activity of the L-type calcium channels. The addition of isradipine in the presence of D2 antagonist in the NAc unmasked a role for the L-type channel which was previously shown to not participate in DA release. These experiments shed some light on the multiple layer of control of the L-type VGCCs in the NAc furthering our understanding of what factors render neurons susceptible to degeneration in PD,