ArticleNaunyn-Schmiedeberg's archives of pharmacology2016
Inhibition of the cardiac Na⁺ channel α-subunit Nav1.5 by propofol and dexmedetomidine.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Effects of dexmedetomidine on cardiac electrophysiology in patients undergoing general anesthesia during perioperative period: a randomized controlled trial.BMC anesthesiology · 2022Trial
- Impact of two sedation protocols on cardiac electrophysiology during spinal anesthesia.Turkish journal of medical sciences · 2026Observational
- Effects and mechanisms of dexmedetomidine preconditioning on isoproterenol-induced ventricular arrhythmias.Scientific reports · 2024Article
- Dexmedetomidine challenge to uncover an intermittent accessory pathway.HeartRhythm case reports · 2024Article
- The feasibility of dexmedetomidine-led anesthesia maintenance strategy during major abdominal surgery.Heliyon · 2024Article
- Prediction of anesthetic torsadogenicity using a human ventricular cell model.Journal of anesthesia · 2023Article
- Comparison of the effects of propofol and alfaxalone on the electrocardiogram of dogs, with particular reference to QT interval.Frontiers in veterinary science · 2023Article
- Effects of Dexmedetomidine on Basic Cardiac Electrophysiology in Adults; a Descriptive Review and a Prospective Case Study.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Transmural conduction delay and block producing a pseudo-infarction electrocardiogram during treatment of anaphylaxis.HeartRhythm case reports · 2022Article
- Local Anesthetic Like Inhibition of the Cardiac NaJournal of experimental pharmacology · 2022Article
- Safe electrophysiologic profile of dexmedetomidine in different experimental arrhythmia models.Scientific reports · 2021Article
- Dexmedetomidine Alleviates Hypoxia-Induced Synaptic Loss and Cognitive Impairment via Inhibition of Microglial NOX2 Activation in the Hippocampus of Neonatal Rats.Oxidative medicine and cellular longevity · 2021Article
- Effects of dexmedetomidine and dexketoprofen on the conduction block of rat sciatic nerve.Neural regeneration research · 2020Article
- Dexmedetomidine Exerted Anti-arrhythmic Effects in Rat With Ischemic Cardiomyopathy via Upregulation of Connexin 43 and Reduction of Fibrosis and Inflammation.Frontiers in physiology · 2020Article
- The Effects of General Anesthetics on Synaptic Transmission.Current neuropharmacology · 2020Review
- Dexmedetomidine enhances tolerance to bupivacaine cardiotoxicity in the isolated rat hearts: alpha 2 adrenoceptors were not involved.BMC pharmacology & toxicology · 2019Article
- Drug-Induced Loss of Preexcitation in Pediatric Patients with WPW Pattern During Electrophysiologic Study.Pediatric cardiology · 2019Article
- Dexmedetomidine Protects Against Chemical Hypoxia-Induced Neurotoxicity in Differentiated PC12 Cells Via Inhibition of NADPH Oxidase 2-Mediated Oxidative Stress.Neurotoxicity research · 2019Article
- The Effects of Intravenous Lipid Emulsion Therapy in the Prevention of Depressive Effects of Propofol on Cardiovascular and Respiratory Systems: An Experimental Animal Study.Medicina (Kaunas, Lithuania) · 2018Article
- Propofol inhibits the voltage-gated sodium channel NaChBac at multiple sites.The Journal of general physiology · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Propofol and dexmedetomidine are very commonly used sedative agents. However, several case reports demonstrated cardiovascular adverse effects of these two sedatives. Both substances were previously demonstrated to quite potently inhibit neuronal voltage-gated Na(+) channels. Thus, a possible molecular mechanism for some of their cardiac side effects is an inhibition of cardiac voltage gated Na(+) channels. In this study, we therefore explored the effects of propofol and dexmedetomidine on the cardiac predominant Na(+) channel α-subunit Nav1.5. Effects of propofol and dexmedetomidine were investigated on constructs of the human α-subunit Nav1.5 stably expressed in HEK-293 cells by means of whole-cell patch clamp recordings. Both agents induced a concentration-dependent tonic inhibition of Nav1.5. The calculated IC50 value for propofol was 228 ± 10 μM, and for dexmedetomidine 170 ± 20 μM. Tonic block only marginally increased on inactivated channels, and a weak use-dependent block at 10 Hz was observed for dexmedetomidine (16 ± 2 % by 100 μM). The voltage dependencies of fast and slow inactivation as well as the time course of recovery from inactivation were shifted by both propofol and dexmedetomidine. Propofol (IC50 126 ± 47 μM) and dexmedetomidine (IC50 182 ± 27 μM) blocked the persistent sodium current induced by veratradine. Finally, the local-anesthetic (LA)-insensitive mutant Nav1.5-F1760A exhibited reduced tonic and use-dependent block by both substances. Dexmedetomidine was generally more potent as compared to propofol. Propofol and dexmedetomidine seem to interact with the LA-binding site to inhibit the cardiac Na(+) channel Nav1.5 in a state-dependent manner. These data suggest that Nav1.5 is a hitherto unrecognized molecular component of some cardiovascular side effects of these sedative agents.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.