Maitotoxin-induced myocardial cell injury: Calcium accumulation followed by ATP depletion precedes cell death

Journal Article · Sun Dec 31 23:00:00 EST 1989 · Toxicology and Applied Pharmacology; (USA)

DOI:https://doi.org/10.1016/0041-008X(90)90093-A· OSTI ID:7244649

Santostasi, G; Kutty, R K; Bartorelli, A L; Yasumoto, T; Krishna, G ^[1]

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1. National Heart, Lung and Blood Institute, Bethesda, MD (USA)

Maitotoxin, the most potent marine toxin, is known to increase the uptake and the accumulation of Ca2+ into cells, and was used in the present study to investigate the mechanisms of myocardial cell damage induced by Ca2+ overload. In cultured cardiomyocytes, isolated from 2-day-old rats, maitotoxin affected cell viability, as indicated by the leakage of the cytosolic enzyme lactate dehydrogenase (LDH) and of radiolabeled adenine nucleotides into the extracellular medium. Maitotoxin-induced leakage of LDH steadily increased between 30 min and 24 hr, and was preceded by a marked depletion of intracellular ATP. Addition of maitotoxin resulted in a rapid influx of extracellular Ca2+, as detected by preincubating the cells in the presence of 45Ca; this effect evolved in a few minutes, thus preceding the signs of cell death. Cytosolic levels of free Ca2+ ((Ca2+)i) were monitored by loading freshly isolated, suspended cardiomyocytes with the intracellular fluorescent probe fura-2; in these cells, maitotoxin induced a dose-dependent increase in (Ca2+)i, with a lag phase of less than a minute. All these effects of maitotoxin were inhibited by reducing Ca2+ concentration in the culture medium or by incubating the cells with the calcium-channel blocking drug verapamil. It is thus demonstrated that maitotoxin-induced cardiotoxicity is secondary to an inordinate influx of Ca2+ into the cells. It is also suggested that, in those conditions that lead to an inordinate accumulation of Ca2+ into myocardial cells, the unmatched demands of energy and the depletion of ATP play a primary role in the irreversible stage of cell damage.

• OSTI ID: 7244649
• Journal Information: Toxicology and Applied Pharmacology; (USA), Journal Name: Toxicology and Applied Pharmacology; (USA) Vol. 102:1; ISSN TXAPA; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
ANIMALS
ANTIGENS
ATP
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL ACCUMULATION
BODY
CALCIUM 45
CALCIUM COMPOUNDS
CALCIUM ISOTOPES
CARDIOVASCULAR SYSTEM
CELL CULTURES
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
ENZYMES
EVEN-ODD NUCLEI
HEART
HEMIACETAL DEHYDROGENASES
INJURIES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LACTATE DEHYDROGENASE
MAMMALS
MATERIALS
MUSCLES
MYOCARDIUM
NUCLEI
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
SURVIVAL TIME
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
VERTEBRATES