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

Journal Article · Mon Jan 01 00:00:00 EST 1990 · 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), Vol. 102:1; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

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