Effects of epoxyeicosatrienoic acids on the cardiac sodium channels in isolated rat ventricular myocytes. 1999

H C Lee, and T Lu, and N L Weintraub, and M VanRollins, and A A Spector, and E F Shibata
Department of Internal Medicine, The University of Iowa College of Medicine, The Veteran Administration Medical Center, Iowa City, IA 52242, USA. hon-chi-lee@uiowa.edu

1. Whole-cell Na+ currents (holding potential, -80 mV; test potential, -30 mV) in rat myocytes were inhibited by 8, 9-epoxyeicosatrienoic acid (8,9-EET) in a dose-dependent manner with 22+/-4% inhibition at 0.5 microM, 48+/-5% at 1 microM, and 73+/-5% at 5 microM (mean +/- S.E.M., n = 10, P<0.05 for each dose vs. control). Similar results were obtained with 5,6-, 11,12-, and 14,15-EETs, while 8,9-dihydroxyeicosatrienoic acid (DHET) was 3-fold less potent and arachidonic acid was 10- to 20-fold less potent. 2. 8,9-EET produced a dose-dependent, hyperpolarized shift in the steady-state membrane potential at half-maximum inactivation (V ), without changing the slope factor. 8,9-EET had no effect on the steady-state activation of Na+ currents. 3. Inhibition of Na+ currents by 8,9-EET was use dependent, and channel recovery was slowed. The effects of 8,9-EET were greater at depolarized potentials. 4. Single channel recordings showed 8,9-EET did not change the conductance or the number of active Na+ channels, but markedly decreased the probability of Na+ channel opening. These results were associated with a decrease in the channel open time and an increase in the channel closed times. 5. Incubation of cultured cardiac myocytes with 1 microM [3H]8,9-EET showed that 25% of the radioactivity was taken up by the cells over a 2 h period, and most of the uptake was incorporated into phospholipids, principally phosphatidylcholine. Analysis of the medium after a 2 h incubation indicated that 86% of the radioactivity remained as [3H]8,9-EET while 13% was converted into [3H]8,9-DHET. After a 30 min incubation, 1-2% of the [3H]8,9-EET uptake by cells remained as unesterified EET. 6. These results demonstrate that cardiac cells have a high capacity to take up and metabolize 8,9-EET. 8,9-EET is a potent use- and voltage-dependent inhibitor of the cardiac Na+ channels through modulation of the channel gating behaviour.

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D006352 Heart Ventricles The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation. Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000831 Animals, Newborn Refers to animals in the period of time just after birth. Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015126 8,11,14-Eicosatrienoic Acid A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5. Homo-gamma Linolenic Acid,8,11,14 Eicosatrienoic Acid,Dihomo-gamma-Linolenic Acid,Dihomogammalinolenic Acid,Ro 12-1989,Dihomo gamma Linolenic Acid,Homo gamma Linolenic Acid,Linolenic Acid, Homo-gamma,Ro 12 1989,Ro 121989
D015222 Sodium Channels Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function. Ion Channels, Sodium,Ion Channel, Sodium,Sodium Channel,Sodium Ion Channels,Channel, Sodium,Channel, Sodium Ion,Channels, Sodium,Channels, Sodium Ion,Sodium Ion Channel

Related Publications

H C Lee, and T Lu, and N L Weintraub, and M VanRollins, and A A Spector, and E F Shibata
April 1993, The American journal of physiology,
H C Lee, and T Lu, and N L Weintraub, and M VanRollins, and A A Spector, and E F Shibata
August 1992, The Journal of pharmacology and experimental therapeutics,
H C Lee, and T Lu, and N L Weintraub, and M VanRollins, and A A Spector, and E F Shibata
December 1983, Circulation research,
H C Lee, and T Lu, and N L Weintraub, and M VanRollins, and A A Spector, and E F Shibata
December 1991, The Journal of general physiology,
H C Lee, and T Lu, and N L Weintraub, and M VanRollins, and A A Spector, and E F Shibata
November 1995, Proceedings of the National Academy of Sciences of the United States of America,
H C Lee, and T Lu, and N L Weintraub, and M VanRollins, and A A Spector, and E F Shibata
March 1994, Zhongguo yao li xue bao = Acta pharmacologica Sinica,
H C Lee, and T Lu, and N L Weintraub, and M VanRollins, and A A Spector, and E F Shibata
July 2014, British journal of pharmacology,
H C Lee, and T Lu, and N L Weintraub, and M VanRollins, and A A Spector, and E F Shibata
June 2007, Chinese medical journal,
H C Lee, and T Lu, and N L Weintraub, and M VanRollins, and A A Spector, and E F Shibata
May 1994, Proceedings. Biological sciences,
H C Lee, and T Lu, and N L Weintraub, and M VanRollins, and A A Spector, and E F Shibata
August 2006, Yao xue xue bao = Acta pharmaceutica Sinica,
Copied contents to your clipboard!