ArticleProceedings of the National Academy of Sciences of the United States of America1998
Muscarinic cholinergic regulation of cardiac myocyte ICa-L is absent in mice with targeted disruption of endothelial nitric oxide synthase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 143 citations in OpenAlex.
- Asymmetric dimethylarginine (ADMA) modulates frequency-dependent muscarinic antagonism of β-adrenergic regulation of rat papillary muscle contractility.Research square · 2026Article
- The Muscarinic Acetylcholine MCells · 2023Article
- The autonomic nervous system and cardiac arrhythmias: current concepts and emerging therapies.Nature reviews. Cardiology · 2019Review
- Cardiac sympatho-vagal balance and ventricular arrhythmia.Autonomic neuroscience : basic & clinical · 2016Review
- Protection against ventricular fibrillation via cholinergic receptor stimulation and the generation of nitric oxide.The Journal of physiology · 2016Article
- Functional expression and modulation of the L-type Ca2+ current in embryonic heart cells.Pediatric cardiology · 2012Article
- Regulation of cardiovascular cellular processes by S-nitrosylation.Biochimica et biophysica acta · 2012Review
- Displacement-encoded and manganese-enhanced cardiac MRI reveal that nNOS, not eNOS, plays a dominant role in modulating contraction and calcium influx in the mammalian heart.American journal of physiology. Heart and circulatory physiology · 2012Article
- Genetic disruption of G proteins, G(i2)alpha or G(o)alpha, does not abolish inotropic and chronotropic effects of stimulating muscarinic cholinoceptors in atrium.British journal of pharmacology · 2009Article
- The exercising heart at altitude.Cellular and molecular life sciences : CMLS · 2009Review
- Nitric oxide signaling and the regulation of myocardial function.Journal of molecular and cellular cardiology · 2008Review
- Endothelial nitric oxide synthase decreases beta-adrenergic responsiveness via inhibition of the L-type Ca2+ current.American journal of physiology. Heart and circulatory physiology · 2008Article
- The placental cholinergic system: localization to the cytotrophoblast and modulation of nitric oxide.Cell communication and signaling : CCS · 2006Article
- S-nitrosothiols modulate G protein-coupled receptor signaling in a reversible and highly receptor-specific manner.BMC cell biology · 2005Article
- Nitric oxide control of cardiac function: is neuronal nitric oxide synthase a key component?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2004Review
- Nitric oxide (NO) is not involved in accentuated antagonism for chronotropy in the isolated mouse atrium.Naunyn-Schmiedeberg's archives of pharmacology · 2004Article
- Reduced left ventricular compliance and mechanical efficiency after prolonged inhibition of NO synthesis in conscious dogs.The Journal of physiology · 2003Article
- Muscarinic regulation of cardiac ion channels.British journal of pharmacology · 2003Review
- Modulation of cardiac contraction, relaxation and rate by the endothelial nitric oxide synthase (eNOS): lessons from genetically modified mice.The Journal of physiology · 2003Review
- Nitric oxide signalling by selective beta(2)-adrenoceptor stimulation prevents ACh-induced inhibition of beta(2)-stimulated Ca(2+) current in cat atrial myocytes.The Journal of physiology · 2002Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Cardiac myocytes have been shown to express constitutively endothelial nitric oxide synthase (eNOS) (nitric oxide synthase 3), the activation of which has been implicated in the regulation of myocyte L-type voltage-sensitive calcium channel current (ICa-L) and myocyte contractile responsiveness to parasympathetic nervous system signaling, although this implication remains controversial. Therefore, we examined the effect of the muscarinic cholinergic agonist carbachol (CCh) on ICa-L and contractile amplitude in isoproterenol (ISO)-prestimulated ventricular myocytes isolated from adult mice, designated eNOSnull mice, with targeted disruption of the eNOS gene. Although both eNOSnull and wild-type (WT) ventricular myocytes exhibited similar increases in ICa-L in response to ISO, there was no measurable suppression of ICa-L by CCh in cells from eNOSnull mice, in contrast to cells from WT mice. These results were reflected in the absence of an effect of CCh on the positive inotropic effect of ISO in eNOSnull myocytes. Also, unlike myocytes from WT animals, eNOSnull myocytes failed to exhibit an increase in cGMP content in response to CCh. Nevertheless, the pharmacologic nitric oxide donors 3-morpholino-sydnonimine and S-nitroso-acetyl-cystein increased cGMP generation and suppressed ISO-augmented ICa-L in eNOSnull cells, suggesting that the signal transduction pathway(s) downstream of eNOS remained intact. Of importance, activation of the acetylcholine-activated K+ channel by CCh was unaffected in atrial and ventricular eNOSnull myocytes. These results confirm the obligatory role of eNOS in coupling muscarinic receptor activation to cGMP-dependent control of ICa-L in cardiac myocytes.
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