ArticleThe Journal of physiology2002
Cocaine binds to a common site on open and inactivated human heart (Na(v)1.5) sodium channels.
Article in The Journal of physiology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 63 citations in OpenAlex.
- Cocaine and the heart - bad news for risk/reward.Journal of molecular and cellular cardiology plus · 2025Article
- Sensory neuron sodium channels as pain targets; from cocaine to Journavx (VX-548, suzetrigine).The Journal of general physiology · 2025Review
- Brugada Phenotype Following a Cocaine Overdose.Cureus · 2024Article
- Stimulant Drugs of Abuse and Cardiac Arrhythmias.Circulation. Arrhythmia and electrophysiology · 2022Review
- Inhibition of Fast Nerve Conduction Produced by Analgesics and Analgesic Adjuvants-Possible Involvement in Pain Alleviation.Pharmaceuticals (Basel, Switzerland) · 2020Review
- The Sigma-1 Receptor: When Adaptive Regulation of Cell Electrical Activity Contributes to Stimulant Addiction and Cancer.Frontiers in neuroscience · 2019Review
- Cocaine Exposure Increases Blood Pressure and Aortic Stiffness via the miR-30c-5p-Malic Enzyme 1-Reactive Oxygen Species Pathway.Hypertension (Dallas, Tex. : 1979) · 2018Article
- State-dependent block of voltage-gated sodium channels by the casein-kinase 1 inhibitor IC261.Investigational new drugs · 2017Article
- Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants.The Journal of general physiology · 2017Article
- A Literature Review of the Use of Sodium Bicarbonate for the Treatment of QRS Widening.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2016Review
- Involvement of reactive oxygen species in cocaine-taking behaviors in rats.Addiction biology · 2015Article
- MTSET modification of D4S6 cysteines stabilize the fast inactivated state of Nav1.5 sodium channels.Frontiers in pharmacology · 2015Article
- Fluoxetine blocks Nav1.5 channels via a mechanism similar to that of class 1 antiarrhythmics.Molecular pharmacology · 2014Article
- Cocaine inhibition of nicotinic acetylcholine receptors influences dopamine release.Frontiers in synaptic neuroscience · 2014Article
- Effects of an epilepsy-causing mutation in the SCN1A sodium channel gene on cocaine-induced seizure susceptibility in mice.Psychopharmacology · 2013Article
- Differential effects of cocaine on dopamine neuron firing in awake and anesthetized rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Article
- Molecular Insights into the Local Anesthetic Receptor within Voltage-Gated Sodium Channels Using Hydroxylated Analogs of Mexiletine.Frontiers in pharmacology · 2012Article
- Y1767C, a novel SCN5A mutation, induces a persistent Na+ current and potentiates ranolazine inhibition of Nav1.5 channels.American journal of physiology. Heart and circulatory physiology · 2011Article
- Molecular determinants of state-dependent block of voltage-gated sodium channels by pilsicainide.British journal of pharmacology · 2010Article
- Fast- or slow-inactivated state preference of Na+ channel inhibitors: a simulation and experimental study.PLoS computational biology · 2010Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
The inhibition by cocaine of the human heart Na+ channel (Na(v)1.5) heterologously expressed in Xenopus oocytes was investigated. Cocaine produced little tonic block of the resting channels but induced a characteristic, use-dependent inhibition during rapid, repetitive stimulation, suggesting that the drug preferentially binds to the open or inactivated states of the channel. To investigate further the state dependence, depolarizing pulses were used to inactivate the channels and promote cocaine binding. Cocaine produced a slow, concentration-dependent inhibition of inactivated channels, which had an apparent K(D) of 3.4 microM. Mutations of the interdomain III-IV linker that remove fast inactivation selectively abolished this high-affinity component of cocaine inhibition, which appeared to be linked to the fast inactivation of the channels. A rapid component of cocaine inhibition persisted in the inactivation-deficient mutant that was enhanced by depolarization and was sensitive to changes in the concentration of external Na+, properties that are consistent with a pore-blocking mechanism. Cocaine induced a use-dependent inhibition of the non-inactivating mutant and delayed the repriming at hyperpolarized voltages, indicating that the drug slowly dissociated when the channels were closed. Mutation of a conserved aromatic residue (Y1767) of the D4S6 segment weakened both the inactivation-dependent and the pore-blocking components of the cocaine inhibition. The data indicate that cocaine binds to a common site located within the internal vestibule and inhibits cardiac Na+ channels by blocking the pore and by stabilizing the channels in an inactivated state.
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