PKA is a tetramer comprising two regulatory subunits and two catalytic subunits. There are four regulatory subunit isoforms (RIα, RIβ, RIIα, RIIβ) and three catalytic isoforms (Cα, Cβ, Cγ); all are widely expressed in the brain.59 As a tetramer, PKA is inactive. Cyclic adenosine 3′, 5′-monophosphate (cAMP), produced by adenylyl cyclase, activates PKA by binding to the regulatory subunits in ways that result in the release and nuclear translocation of active catalytic subunits.63 PKA activity can be measured as increased PKA catalytic subunit translocation63 or as increased PKA-mediated phosphorylation of specific substrates such as the α-amino-3-hydroxy-5-methyl-isoxazolepropionic acid (AMPA) receptor GluR1 subunit Ser-84564 or the NMDA receptor NR1 subunit Ser-897.65
