Subcellular postsynaptic density

The C and R subunits are encoded by three (a, (3, y) and four (lot, 1(3, Hot, 11(3) genes, respectively (Tasken et al., 1997). In striatal areas, Ca, C(3 and RII(3 are the predominantly expressed isoforms (Brandon et al., 1997). The mice deficient in functional RII(3 subunit show a decreased PKA activity in the striatum and exhibit behavioral modifications that suggest an alteration in their dopamine neurotransmission (Brandon et al., 1998). In neurons, the presence of RII targets the PKA towards the postsynaptic densities whereas PKA containing RI subunits are essentially localized in the cytoplasm (Corbin et al., 1977 Deviller et al., 1984). The association of RII subunits with these subcellular compartments is due to their interaction with A kinase attachment proteins (AKAP) (Carr et al., 1992 ... 

When an action potential traveling down the axon of a motoneuron reaches the myoneural endplate, a process occurs that releases acetylcholine into the synaptic cleft and consequently depolarizes the postsynaptic membrane. A similar process probably occurs at cholinergic synapses in the central nervous system. In 1950 Fatt and Katz discovered a spontaneous subthreshold activity (MEPP) of motor nerve endings and were thereby led to the concept that acetylcholine is released in definite units (quanta) of 10 to 10 molecules. Electron microscopy subsequently revealed characteristic vesicles about 40 nm in diameter, clustered near presynaptic membranes. Subcellular fractionation procedures were devised by Whittaker and de Robertis for the isolation of these vesicles from brain homogenates in sucrose density gradients, and it was soon demonstrated that they were indeed concentrated reservoirs of acetylcholine. The hypothesis that the vesicles discharge the quanta of transmitter became irresistible. 

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