NO ARREST NEEDED TO PREVENT CARDIAC ARREST

Abstract

Most vertebrates die within a few minutes when deprived of molecular oxygen(anoxia) because the heart and brain depend on a continuous supply of oxygen. However, some cold-blooded vertebrates are remarkably anoxia-tolerant and can survive for months without oxygen. One of the keys to surviving prolonged anoxia is being able to balance energy supply and demand. One way to achieve this is to reduce energy-consuming processes of cells to a level that can be supported by the decreased amount of energy available from anaerobic respiration. Since ion pumping is energetically costly, energy can potentially be conserved by reducing the density of cellular membrane ion transport channels in excitable tissues such as the heart. Matti Vornanen and Vesa Paajanen of the University of Joensuu, Finland, set out to test this `channel arrest' hypothesis in the crucian carp (Carassius carassius), an extremely anoxia-tolerant fish that spends a third of its life in anoxic water under the ice of shallow Finno-Scandinavian ponds.The oxygen content of the water in the ponds where crucian carp live is too low for the fish to produce energy aerobically for five and a half months throughout the winter, so carp need to conserve energy during winter. Vornanen and Paajenen reasoned that since L-type Ca2+ channels regulate the force of heart muscle contraction through changes in the amount of free intracellular Ca2+, these channels are good targets for channel arrest. They hypothesized that, if crucian carp use channel arrest to conserve energy during anoxia in winter, the number of dihydropyridine receptors(subunit of the L-type Ca2+ cardiac channel that triggers channel opening) and density of L-type Ca2+ current should both be decreased in winter-captured, anoxic carp compared with summer-captured,normoxic animals.Vornanen and Paajanen captured wild carp monthly throughout an entire year and measured the number of dihydropyridine receptors and the density of L-type Ca2+ current in the ventricles of the carp's hearts to see how these changed with the seasons. Unexpectedly, they found that the number of dihydropyridine receptors in winter fish was the same as in summer fish. Thus,cardiac L-type Ca2+ channels were not downregulated by seasonal anoxia in the natural environment, suggesting that carp do not use differential expression of the Ca2+ channel protein to save energy in ion pumping or in reduced cardiac contractility during anoxia. This finding, in conjunction with the team's earlier finding that inward rectifier K+ current density of crucian carps' heart cells is also unaffected by prolonged anoxia, led Vornanen and Paajanen to conclude that crucian carp do not use channel arrest as an energy-conserving mechanism in the heart during prolonged anoxia.However, Vornanen and Paajanen did observe a 6.1-fold reduction in Ca2+ current in winter compared with summer fish, indicating that low temperatures depress Ca2+ current. They suggest that when temperatures drop, the resulting decreased Ca2+ current may allow for sufficient savings in ATP-dependent ion pumping and reduced cardiac contractility to attain a balance between energy supply and demand, providing protection against anoxia.