This study focuses on the investigation of expression and function of N-methyl D-aspartate receptors (NMDARs) in rat myocardium and on the role these receptors play in control of autonomous heart function. NMDARs are ionotropic glutamate receptors mediating Ca2+ uptake upon their activation by co-agonists glutamate and glycine. We have detected the presence of gene transcripts of the NR1, 2A, B, C and D and 3A subunits. Expression of the NMDAR subunits and activity of the receptor complex varied substantially within the heart. In hearts of young animals maximal expression and the highest density of active NMDAR units was found in the atria and in septum. In senescent hearts up-regulation in NR2B abundance and the receptor activity was observed in the ventricles. Activation of the NMDARs in isolated ventricular myocytes resulted in an increase in the intracellular Ca2+ levels and initiation of Ca2+ transients which could be suppressed by co-administration of antagonist of the NMDAR, MK-801. Perfusion of rat hearts with autologous blood supplemented with NMDA agonists was associated with induction of tachycardia and sinus arrhythmia, and a positive inotropic effect whereas intracoronary administration of the NMDAR antagonists exerted an anti-arrhythmic effect and resulted in bradycardia. We have performed pilot studies exploring expression levels of the NMDAR subunits in biopsies collected from all four chambers of human patients undergoing mitral valve replacement surgery. Expression of NR1, NR2A, B, C and D, NR3A and B was shown. Development of decompensated hypertrophy was associated with an increase in expression. The obtained data reveal that NMDARs are expressed in rat heart and are active players in calcium handling contributing to the pacemaker function and contractile force control.
N-methyl D-aspartate (NMDA) receptors in rat and human heart
Kosenkov, Dmitry;FAGGIAN, Giuseppe
2013-01-01
Abstract
This study focuses on the investigation of expression and function of N-methyl D-aspartate receptors (NMDARs) in rat myocardium and on the role these receptors play in control of autonomous heart function. NMDARs are ionotropic glutamate receptors mediating Ca2+ uptake upon their activation by co-agonists glutamate and glycine. We have detected the presence of gene transcripts of the NR1, 2A, B, C and D and 3A subunits. Expression of the NMDAR subunits and activity of the receptor complex varied substantially within the heart. In hearts of young animals maximal expression and the highest density of active NMDAR units was found in the atria and in septum. In senescent hearts up-regulation in NR2B abundance and the receptor activity was observed in the ventricles. Activation of the NMDARs in isolated ventricular myocytes resulted in an increase in the intracellular Ca2+ levels and initiation of Ca2+ transients which could be suppressed by co-administration of antagonist of the NMDAR, MK-801. Perfusion of rat hearts with autologous blood supplemented with NMDA agonists was associated with induction of tachycardia and sinus arrhythmia, and a positive inotropic effect whereas intracoronary administration of the NMDAR antagonists exerted an anti-arrhythmic effect and resulted in bradycardia. We have performed pilot studies exploring expression levels of the NMDAR subunits in biopsies collected from all four chambers of human patients undergoing mitral valve replacement surgery. Expression of NR1, NR2A, B, C and D, NR3A and B was shown. Development of decompensated hypertrophy was associated with an increase in expression. The obtained data reveal that NMDARs are expressed in rat heart and are active players in calcium handling contributing to the pacemaker function and contractile force control.
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