Parvalbumin selectivity

Zhang ZJ, Reynolds GP. 2000. A selective deficit in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia. Schizophr Res 49 65. 

Redesign of Ca fMg Specificity. Proteins in the calmodulin superfamily (including troponin C, parvalbumin (PV) and oncomodulin (OM)) share similar overall structure and yet have different selectivity for Ca and Mg see Calcium-binding Proteins, Cation-activated Enzymes). For example, PV and OM have four helix-tum-helix domains, two of which contain mixed Ca /Mg sites and two Ca -specific sites. The mixed Ca /Mg sites have been converted to Ca -specific sites by replacing amino acids with the corresponding residues in the Ca -specific site. " ... 

Candidate transmitters in AON and other olfactory cortical areas are summarized in Table 4. Aspartate has been proposed as a transmitter of AON neurons (mainly the dorsal and external divisions of AON) based on selective retrograde transport of H aspartate (Watanabe and Kawana, 1984 Fuller and Price, 1988). Fewer neurons in other subdivisions of AON contain aspartate, and no neurons in other known afferents to the bulb contain aspartate. There are a few met-enkephalin and somatostatinergic neurons in AON and some of these appear to project to the olfactory bulb (Davis et al. 1982). It appears that all neurons in AONpE contain the neuropeptide CRF (Shipley, in preparation). Besides the neurotransmitters/peptides discussed above, immunoreac-tive cells and fibers to calcium binding proteins have been described in AON. In this respect, calretinin immunoreactive fibers are found in the molecular layer of AON (Jacobowitz and Winsky, 1991), calbindin positive cells are found in all subdivisions of AON (Garcia-Ojeda et al. 1992 Celio, 1990) while parvalbumin positive cells are found in all subdivisions except for the medial one where the cells are quite sparse (Garcia-Ojeda et al. 1992 Celio, 1990). 

The hypotheses rest on the accuracy of the model for parvalbumin and the reliability of the VDW parameters used as these are refined the hypothesis will have to be reviewed. The lessons for the design of Ca selective ligands are obvious, but the synthetic problems are considerable and may be more amenable to genetic engineering on CD and EF type loops. 

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