Header

UZH-Logo

Maintenance Infos

Cardiac N-methyl D-aspartate receptors as a pharmacological target


Makhro, Asya; Tian, Qinghai; Kaestner, Lars; Kosenkov, Dmitry; Faggian, Giuseppe; Gassmann, Max; Schwarzwald, Colin; Bogdanova, Anna (2016). Cardiac N-methyl D-aspartate receptors as a pharmacological target. Journal of Cardiovascular Pharmacology, 68(5):356-373.

Abstract

This study focuses on characterization of the cardiac N-methyl D-aspartate receptors (NMDARs) as a target for endogenous and synthetic agonists and antagonists. Using isolated perfused rat hearts, we have shown that intracoronary administration of the NMDAR agonists and antagonists has a pronounced effect on autonomous heart function. Perfusion of rat hearts with autologous blood supplemented with NMDAR agonists was associated with induction of tachycardia, sinus arrhythmia and ischemia occurring within physiological plasma concentration range for glutamate and glycine. Intracoronary administration of the NMDAR antagonists exerted an anti-arrhythmic effect and resulted in bradycardia and improvement of capillary perfusion. Action of antagonists eliprodil, Ro25-6981, memantine, ketamine, and MK-801 on autonomous heart function diverged strikingly from that of L-type Ca channel blockers. Cardiac NMDAR subunit composition differed from that of neuronal receptors and was age- and chamber-specific. Transcripts of the GluN3A and GluN2D were found in all heart chambers, whereas expression of GluN1 and GluN2A and 2C were restricted to the atria. Expression of the GluN2B protein in ventricles increased markedly with age of the animals. The obtained data reveal that NMDARs are expressed in rat heart contributing to the autonomic heart rate regulation and the function of the cardiac conduction system.

Abstract

This study focuses on characterization of the cardiac N-methyl D-aspartate receptors (NMDARs) as a target for endogenous and synthetic agonists and antagonists. Using isolated perfused rat hearts, we have shown that intracoronary administration of the NMDAR agonists and antagonists has a pronounced effect on autonomous heart function. Perfusion of rat hearts with autologous blood supplemented with NMDAR agonists was associated with induction of tachycardia, sinus arrhythmia and ischemia occurring within physiological plasma concentration range for glutamate and glycine. Intracoronary administration of the NMDAR antagonists exerted an anti-arrhythmic effect and resulted in bradycardia and improvement of capillary perfusion. Action of antagonists eliprodil, Ro25-6981, memantine, ketamine, and MK-801 on autonomous heart function diverged strikingly from that of L-type Ca channel blockers. Cardiac NMDAR subunit composition differed from that of neuronal receptors and was age- and chamber-specific. Transcripts of the GluN3A and GluN2D were found in all heart chambers, whereas expression of GluN1 and GluN2A and 2C were restricted to the atria. Expression of the GluN2B protein in ventricles increased markedly with age of the animals. The obtained data reveal that NMDARs are expressed in rat heart contributing to the autonomic heart rate regulation and the function of the cardiac conduction system.

Statistics

Altmetrics

Downloads

59 downloads since deposited on 30 Aug 2016
49 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
05 Vetsuisse Faculty > Veterinary Clinic > Equine Department
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:10 August 2016
Deposited On:30 Aug 2016 14:27
Last Modified:08 Dec 2017 20:17
Publisher:Lippincott Williams & Wilkins
ISSN:0160-2446
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1097/FJC.0000000000000424
PubMed ID:27525575

Download

Download PDF  'Cardiac N-methyl D-aspartate receptors as a pharmacological target'.
Preview
Content: Accepted Version
Filetype: PDF
Size: 12MB
View at publisher
Download PDF  'Cardiac N-methyl D-aspartate receptors as a pharmacological target'.
Preview
Content: Accepted Version
Filetype: PDF
Size: 13MB