Protective effect of eicosapentaenoic acid on ouabain toxicity in neonatal rat cardiac myocytes
- Harvard Medical School, Boston, MA (USA)
- Univ. Munchen, (Germany)
- Brigham and Women's Hospital, Boston, MA (USA)
Isolated neonatal cardiac myocytes have been utilized as a model for the study of cardiac arrhythmogenic factors. The myocytes respond to the toxic effects of a potent cardiac glycoside, ouabain at 0.1 mM, by an increase in their spontaneous beating rate and a reduction in amplitude of contractions resulting within minutes in a lethal state of contracture. Incubating the isolated myocytes for 3{endash}5 days in culture medium enriched with 5 {mu}M arachidonic acid had no effect on the development of lethal contracture after subsequent exposure to 0.1 mM ouabain. By contrast, incubating the myocytes for 3{endash}5 days with 5 {mu}M eicosapentaenoic acid completely prevented the toxic effects of ouabain at 0.1 mM. No differences in bumetanide-inhibitable {sup 86}Rb flux were observed between the three preparations. However, measurements with fura-2 of cytosolic free calcium levels indicated that control and arachidonic acid-enriched myocytes developed toxic cytosolic calcium concentrations of 845 {plus minus} 29 and 757 {plus minus} 64 nM, respectively, on exposure to 0.1 mM ouabain, whereas in eicosapentaenoic acid-enriched myocytes, physiologic calcium levels were preserved. Incubating the myocytes with eicosapentaenoic acid for 3{endash}5 days resulted in a small reduction of arachidonic acid and a small but significant increase of eicosapentaenoic acid in membrane phospolipids of the myocytes.
- OSTI ID:
- 5584190
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:20; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
EICOSANOIC ACID
BIOLOGICAL EFFECTS
OUABAIN
TOXICITY
RUBIDIUM 86
MEMBRANE TRANSPORT
ATP-ASE
CALCIUM COMPOUNDS
ENZYME ACTIVITY
HEART
MYOCARDIUM
PHOSPHOLIPIDS
SOMATIC CELLS
ACID ANHYDRASES
ALKALI METAL ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
CARBOXYLIC ACIDS
CARDIAC GLYCOSIDES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
DAYS LIVING RADIOISOTOPES
DRUGS
ENZYMES
ESTERS
GLYCOSIDES
HYDROLASES
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LIPIDS
MINUTES LIVING RADIOISOTOPES
MONOCARBOXYLIC ACIDS
MUSCLES
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHOSPHOHYDROLASES
RADIOISOTOPES
RUBIDIUM ISOTOPES
STROPHANTHINS
550201* - Biochemistry- Tracer Techniques