ArticleThe Journal of general physiology2001
Effects of dantrolene on steps of excitation-contraction coupling in mammalian skeletal muscle fibers.
Article in The Journal of general physiology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 85 citations in OpenAlex.
- A phase Ib/IIa clinical trial of dantrolene sodium in patients with Wolfram syndrome.JCI insight · 2021Trial
- Crystal structures of Ryanodine Receptor reveal dantrolene and azumolene interactions guiding inhibitor development.Nature communications · 2025Article
- Discovery and Treatment of Action Potential-Independent Myotonia in Hyperkalemic Periodic Paralysis.Annals of clinical and translational neurology · 2025Article
- Reciprocal rescue of Wolfram syndrome by two causative genes.EMBO reports · 2025Article
- Molecular Aspects Implicated in Dantrolene Selectivity with Respect to Ryanodine Receptor Isoforms.International journal of molecular sciences · 2023Article
- Wolfram Syndrome 1: A Pediatrician's and Pediatric Endocrinologist's Perspective.International journal of molecular sciences · 2023Review
- Metabolic Treatment of Wolfram Syndrome.International journal of environmental research and public health · 2022Review
- Honey bees long-lasting locomotor deficits after exposure to the diamide chlorantraniliprole are accompanied by brain and muscular calcium channels alterations.Scientific reports · 2019Article
- Sodium current inhibition following stimulation of exchange protein directly activated by cyclic-3',5'-adenosine monophosphate (Epac) in murine skeletal muscle.Scientific reports · 2019Article
- Crosstalk between Calcium and ROS in Pathophysiological Conditions.Oxidative medicine and cellular longevity · 2019Review
- Reduced threshold for store overload-induced CaThe Biochemical journal · 2017Article
- Mind the magnesium, in dantrolene suppression of malignant hyperthermia.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Dantrolene requires MgProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Antioxidants protect calsequestrin-1 knockout mice from halothane- and heat-induced sudden death.Anesthesiology · 2015Article
- Osmosensation in TRPV2 dominant negative expressing skeletal muscle fibres.The Journal of physiology · 2015Article
- Essential Role of Calmodulin in RyR Inhibition by Dantrolene.Molecular pharmacology · 2015Article
- The couplonopathies: A comparative approach to a class of diseases of skeletal and cardiac muscle.The Journal of general physiology · 2015Review
- Altered Ca(2+) signaling in skeletal muscle fibers of the R6/2 mouse, a model of Huntington's disease.The Journal of general physiology · 2014Article
- Characterization of ryanodine receptor type 1 single channel activity using "on-nucleus" patch clamp.Cell calcium · 2014Article
- Accelerated activation of SOCE current in myotubes from two mouse models of anesthetic- and heat-induced sudden death.PloS one · 2013Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The effects of the muscle relaxant dantrolene on steps of excitation-contraction coupling were studied on fast twitch muscles of rodents. To identify the site of action of the drug, single fibers for voltage-clamp measurements, heavy SR vesicles for calcium efflux studies and solubilized SR calcium release channels/RYRs for lipid bilayer studies were isolated. Using the double Vaseline-gap or the silicone-clamp technique, dantrolene was found to suppress the depolarization-induced elevation in intracellular calcium concentration ([Ca2+]i) by inhibiting the release of calcium from the SR. The suppression of [Ca2+]i was dose-dependent, with no effect at or below 1 microM and a 53 +/- 8% (mean +/- SEM, n = 9, cut fibers) attenuation at 0 mV with 25 microM of extracellularly applied dantrolene. The drug was not found to be more effective if injected than if applied extracellularly. Calculating the SR calcium release revealed an equal suppression of the steady (53 +/- 8%) and of the early peak component (46 +/- 6%). The drug did not interfere with the activation of the voltage sensor in as much as the voltage dependence of both intramembrane charge movements and the L-type calcium currents (I(Ca)) were left, essentially, unaltered. However, the inactivation of I(Ca) was slowed fourfold, and the conductance was reduced from 200 +/- 16 to 143 +/- 8 SF(-1) (n = 10). Dantrolene was found to inhibit thymol-stimulated calcium efflux from heavy SR vesicles by 44 +/- 10% (n = 3) at 12 microM. On the other hand, dantrolene failed to affect the isolated RYR incorporated into lipid bilayers. The channel displayed a constant open probability for as long as 30-50 min after the application of the drug. These data locate the binding site for dantrolene to be on the SR membrane, but be distinct from the purified RYR itself.
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