HGNC Approved Gene Symbol: PVALB
Cytogenetic location: 22q12.3 Genomic coordinates (GRCh38): 22:36,800,703-36,819,499 (from NCBI)
Parvalbumin, a high affinity calcium-ion binding protein, is expressed in high levels only in fast-contracting muscles and at lower levels in brain and several endocrine tissues. It is related in structure and function to calmodulin (114180) and troponin C (191040), with which its gene constitutes a superfamily. Berchtold et al. (1987) determined the structure of the rat parvalbumin gene.
Heart failure frequently involves diastolic dysfunction that is characterized by a prolonged relaxation. This prolonged relaxation is typically the result of a decreased rate of intracellular Ca(2+) sequestration. As an approach to possible correction of diastolic dysfunction, Wahr et al. (1999) hypothesized that expression of the Ca(2+)-binding protein parvalbumin in cardiac myocytes would lead to increased rates of Ca(2+) sequestration and mechanical relaxation. Parvalbumin, which is normally absent in cardiac tissue, is known to act as a soluble relaxing factor in fast skeletal muscle fibers by acting as a delayed Ca(2+) sink. As a test of the hypothesis, Wahr et al. (1999) used gene transfer to express parvalbumin in isolated adult cardiac myocytes. They found that expression of parvalbumin dramatically increased the rate of Ca(2+) sequestration and the relaxation rate in normal cardiac myocytes. Importantly, parvalbumin fully restored the relaxation rate in diseased cardiac myocytes isolated from an animal model of human diastolic dysfunction.
Parvalbumin is not naturally expressed in the heart. In rats, Szatkowski et al. (2001) showed that parvalbumin gene transfer to the heart in vivo produced levels of parvalbumin characteristic of fast skeletal muscles, caused a physiologically relevant acceleration of heart relaxation performance in normal hearts, and enhanced relaxation performance in an animal model of slowed cardiac muscle relaxation. They suggested that parvalbumin may offer the unique potential to correct defective relaxation in energetically compromised failing hearts because the relaxation-enhancement effect of parvalbumin arises from an ATP-independent mechanism.
Abuse of the dissociative anesthetic ketamine can lead to a syndrome indistinguishable from schizophrenia. In animals, repetitive exposure to this N-methyl-D-aspartate receptor antagonist induced the dysfunction of a subset of cortical fast-spiking inhibitory interneurons, with loss of expression of parvalbumin and the gamma-aminobutyric acid-producing enzyme GAD67 (605363). Behrens et al. (2007) showed that exposure of mice to ketamine induced a persistent increase in brain superoxide due to activation in neurons of reduced NADPH oxidase (300225). Decreasing superoxide production prevented the effects of ketamine on inhibitory interneurons in the prefrontal cortex. Behrens et al. (2007) concluded that their results suggested that NADPH oxidase may represent a novel target for the treatment of ketamine-induced psychosis.
Donato et al. (2013) showed that environmental enrichment and Pavlovian contextual fear conditioning induce opposite, sustained, and reversible hippocampal parvalbumim (PV) network configurations in adult mice. Specifically, enrichment promotes the emergence of large fractions of low differentiation (low PV and GAD67 (605363) expression) basket cells with low excitatory-to-inhibitory synaptic density ratios, whereas fear conditioning leads to large fractions of high differentiation (high PV and GAD67 expression) basket cells with high excitatory-to-inhibitory synaptic density ratios. Pharmacogenetic inhibition or activation of PV neurons was sufficient to induce such opposite low-PV-network or high-PV-network configurations, respectively. The low-PV-network configuration enhanced structural synaptic plasticity, and memory consolidation and retrieval, whereas these were reduced by the high-PV-network configuration. Donato et al. (2013) then showed that maze navigation learning induces a hippocampal low-PV-network configuration paralleled by enhanced memory and structural synaptic plasticity throughout training, followed by a shift to a high-PV-network after learning completion. The shift to a low-PV-network configuration specifically involved increased vasoactive intestinal peptide (VIP; 192320)-positive GABAergic boutons and synaptic transmission onto PV neurons. Closely comparable low- and high-PV-network configurations involving VIP boutons were specifically induced in primary motor cortex upon rotarod motor learning. Donato et al. (2013) concluded that their results uncovered a network plasticity mechanism induced after learning through VIP-PV microcircuit modulation, and involving large, sustained, and reversible shifts in the configuration of PV basket cell networks in the adult.
Berchtold et al. (1987) used the rat gene to assign the human PVALB gene to chromosome 22, by Southern analysis of DNA from somatic cell hybrids. The assignment was confirmed and regionalized by dosage analysis of cell lines with haploid or triploid copy number for part of chromosome 22. Cells from a patient with the DiGeorge syndrome (188400) and deletion of the 22q11.2 segment had decreased dosage of the parvalbumin gene.
Zuhlke et al. (1989) mapped the mouse parvalbumin gene (Pva) to chromosome 15. By linkage and by in situ hybridization, Schoffl and Jockusch (1990) mapped the Pva gene to a region on mouse chromosome 15 that is homologous to a region on human chromosome 22. Using somatic cell hybrids containing parts of human chromosome 22, Ritzler et al. (1992) sublocalized the PVALB gene to 22q12-q13.1.
Behrens, M. M., Ali, S. S., Dao, D. N., Lucero, J., Shekhtman, G., Quick, K. L., Dugan, L. L. Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase. Science 318: 1645-1647, 2007. [PubMed: 18063801] [Full Text: https://doi.org/10.1126/science.1148045]
Berchtold, M. W., Epstein, P., Beaudet, A. L., Payne, M. E., Heizmann, C. W., Means, A. R. Structural organization and chromosomal assignment of the parvalbumin gene. J. Biol. Chem. 262: 8696-8701, 1987. [PubMed: 3036821]
Donato, F., Rompani, S. B., Caroni, P. Parvalbumin-expressing basket-cell network plasticity induced by experience regulates adult learning. Nature 504: 272-276, 2013. [PubMed: 24336286] [Full Text: https://doi.org/10.1038/nature12866]
Ritzler, J. M., Sawhney, R., Geurts van Kessel, A. H. M., Grzeschik, K.-H., Schinzel, A., Berchtold, M. W. The genes for the highly homologous Ca(2+)-binding proteins oncomodulin and parvalbumin are not linked in the human genome. Genomics 12: 567-572, 1992. [PubMed: 1559707] [Full Text: https://doi.org/10.1016/0888-7543(92)90449-3]
Schoffl, F., Jockusch, H. Genetic mapping and physical characterization of parvalbumin genes. Int. J. Biochem. 22: 1211-1215, 1990. [PubMed: 2257946] [Full Text: https://doi.org/10.1016/0020-711x(90)90300-r]
Szatkowski, M. L., Westfall, M. V., Gomez, C. A., Wahr, P. A., Michele, D. E., DelloRusso, C., Turner, I. I., Hong, K. E., Albayya, F. P., Metzger, J. M. In vivo acceleration of heart relaxation performance by parvalbumin gene delivery. J. Clin. Invest. 107: 191-198, 2001. [PubMed: 11160135] [Full Text: https://doi.org/10.1172/JCI9862]
Wahr, P. A., Michele, D. E., Metzger, J. M. Parvalbumin gene transfer corrects diastolic dysfunction in diseased cardiac myocytes. Proc. Nat. Acad. Sci. 96: 11982-11985, 1999. [PubMed: 10518562] [Full Text: https://doi.org/10.1073/pnas.96.21.11982]
Zuhlke, C., Schoffl, F., Jockusch, H., Simon, D., Guenet, J.-L. cDNA sequence and chromosomal localization of the mouse parvalbumin gene, Pva. Genet. Res. 54: 37-43, 1989. [PubMed: 2572511] [Full Text: https://doi.org/10.1017/s0016672300028354]