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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.
