Figure 8.

Dopamine modulates two types of K⁺ currents in PFC neurons. DA modulates the VGKC and the IRKC via activation of DA D₁- and D₂-class receptors. Activation of D₁R increases intracellular cAMP level by activation of adenylyl cyclase (AC). The intracellular cAMP may diverge into two pathways: (1) direct interaction with IRK channels and reduction of IRKC; (2) PKA-dependent phosphorylation of IRK channels and enhancement of the IRKC. Although D₁R-mediated modulation of IRKC is bidirectional, the inhibitory effect predominates under normal conditions. Activation of D₂R inhibits the adenylyl cyclase activity, reduces basal activity of the cAMP–PKA signal transduction pathway, and dephosphorylates IRK channels, resulting in suppression of IRKC. DA modulates the VGKC primarily through D₁R, the activation of which stimulates the adenylyl cyclase–cAMP–PKA pathway and increases the phosphorylation of VGK channels, resulting in suppression of the D-type VGKC. P, Phosphorylation.