Role of N-methyl D-aspartate (NMDA) receptors in zebrafish heart development and function

posted Jan 25, 2017, 11:24 PM by sourav ghosh
Sridhar Sivasubbu
CSIR-Institute of Genomics & Integrative Biology, New Delhi, India

NMDA receptors (NMDAR) are a subtype of ionotropic glutamate receptors mediating calcium uptake upon their activation by co-agonists glutamate and glycine. NMDAR exhibit distinct patterns of developmental expression in the central nervous system. However their role in heart development and function remains elusive. We employed a gene trapping based insertional mutagenesis approach to isolate zebrafish mutant animals that displayed pronounced cardiac arrhythmia followed by chamber enlargement and cardiac hypertrophy. Owing to the phenotype of an enlarged heart, we have named this mutant as bigheart (bh). The mutation in bh, maps to an intron of the NMDAR gene family member that forms calcium permeable ion channels. Our investigation revealed the presence of a novel transcript within the intron of the NMDAR gene. We name this transcript as NMDAR Associated RNA Transcript (NMDAR-ART). We characterized the novel transcript and shown that the NMDAR-ART is a putative long non-coding RNA (lncRNA). bh mutant zebrafish embryos and adults exhibited calcium handling defects and differential expression of calcium handling genes as well as cardiac remodelling markers were also documented. In summary, we report the identification of a novel lncRNA transcript called NMDAR-ART that expresses in specific zebrafish heart chambers. We show that NMDAR-ART has a potential role in cardiac rhythm function by regulating calcium flux. We hypothesize that NMDAR-ART regulates key calcium handling genes for maintaining intracellular calcium homeostasis in the zebrafish heart.