APA
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Moshal, K., Kumar, M., Tyagi, N., Mishra, P., Metreveli, N. S., Rodríguez, W., & Tyagi, S. (2009). Restoration of contractility in hyperhomocysteinemia by cardiac-specific deletion of NMDA-R1. American Journal of Physiology. Heart and Circulatory Physiology.
Chicago/Turabian
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Moshal, K., Munish Kumar, N. Tyagi, P. Mishra, Naira S. Metreveli, W. Rodríguez, and S. Tyagi. “Restoration of Contractility in Hyperhomocysteinemia by Cardiac-Specific Deletion of NMDA-R1.” American Journal of Physiology. Heart and Circulatory Physiology (2009).
MLA
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Moshal, K., et al. “Restoration of Contractility in Hyperhomocysteinemia by Cardiac-Specific Deletion of NMDA-R1.” American Journal of Physiology. Heart and Circulatory Physiology, 2009.
BibTeX Click to copy
@article{k2009a,
title = {Restoration of contractility in hyperhomocysteinemia by cardiac-specific deletion of NMDA-R1.},
year = {2009},
journal = {American Journal of Physiology. Heart and Circulatory Physiology},
author = {Moshal, K. and Kumar, Munish and Tyagi, N. and Mishra, P. and Metreveli, Naira S. and Rodríguez, W. and Tyagi, S.}
}
Homocysteine (HCY) activated mitochondrial matrix metalloproteinase-9 and led to cardiomyocyte dysfunction, in part, by inducing mitochondrial permeability (MPT). Treatment with MK-801 [N-methyl-d-aspartate (NMDA) receptor antagonist] ameliorated the HCY-induced decrease in myocyte contractility. However, the role of cardiomyocyte NMDA-receptor 1 (R1) activation in hyperhomocysteinemia (HHCY) leading to myocyte dysfunction was not well understood. We tested the hypothesis that the cardiac-specific deletion of NMDA-R1 mitigated the HCY-induced decrease in myocyte contraction, in part, by decreasing nitric oxide (NO). Cardiomyocyte-specific knockout of NMDA-R1 was generated using cre/lox technology. NMDA-R1 expression was detected by Western blot and confocal microscopy. MPT was determined using a spectrophotometer. Myocyte contractility and calcium transients were studied using the IonOptix video-edge detection system and fura 2-AM loading. We observed that HHCY induced NO production by agonizing NMDA-R1. HHCY induced the MPT by agonizing NMDA-R1. HHCY caused a decrease in myocyte contractile performance, maximal rate of contraction and relaxation, and prolonged the time to 90% peak shortening and 90% relaxation by agonizing NMDA-R1. HHCY decreased contraction amplitude with the increase in calcium concentration. The recovery of calcium transient was prolonged in HHCY mouse myocyte by agonizing NMDA-R1. It was suggested that HHCY increased mitochondrial NO levels and induced MPT, leading to the decline in myocyte mechanical function by agonizing NMDA-R1.