Autocatalytic pathways to cell death: A new analysis of the tuna burn problem.
During capture and storage of tuna, a small but significant number of fish display a characteristic muscle degeneration termed tuna burn. Based on detailed amino acid analyses and on previous studies of metabolite changes during online swimming of tuna, a new model of the etiology of burnt muscle is developed. According to this model oxygen-lack to white muscle (developing initially during capture) leads to a metabolic collapse, to a drop in ATP concentration, to a consequent opening of ATP-dependent K(+) channels, with an efflux of K(+), and thus to a collapse of membrane potential. When the membrane potential falls far enough to open voltage-dependent Ca(++) channels, Ca(++) influx occurs leading to elevated Ca(++) concentrations in the cytosol. This process is augmented by simultaneous movement of Ca(++) from sarcoplasmic reticulum (SR) and from mitochondria into the cytosol. At high intracellular concentrations Ca(++) can be devastating. One of its more notable effects involves the activation of Ca(++)-dependent proteases, which preferentially target key components of the contractile machinery (troponins, tropomyosin, C-protein, M-protein, Z-discs, α-actinin) and thus cause disassembly of myofilaments prior to any significant hydrolysis of myosin or actin. This process is autocatalytic in the sense that Ca(++)-activated proteases may act upon SR, thus increasing Na(+) /Ca(++) exchange, and ultimately adding more Ca(++) to the cytosolic pool. According to this model, the difference between burnt and unburnt regions of the myotome is simply due to how far each region has moved along this self-destructive, autocatalytic pathway. The model is helpful in explaining previously perplexing data and in making useful (i.e. measurable) predictions for further studies of this important problem.
Natl. Marine Fisheries Service, NOAA, 96822, Honolulu, Hawaii.
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Hochachka
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Brill