Cold tolerance in mammalian cells.

As whole organisms, most mammals have a poor tolerance for hypothermia. But their cells may have a capacity for a far wider cold tolerance, which may be expressed in peripheral tissues, sporadically in core tissue and in cultured cells. Against this background the cold resistance of cells of deep hibernators may be seen as the extreme of a continuum and is complicated by the consideration that the voluntary hypothermia of hibernation is probably in most cases a metabolic adaptation to forestall starvation. Similarly, cold resistance of peripheral tissues may in diving animals be confounded by the need to be adapted to hypoxia as well. Hence, attempts to analyse cold resistance by comparisons of absolute rates of arbitrarily chosen reactions may be misleading. A more useful approach is analysis of maintenance of balance: balance between ATP synthesis and utilization, balance between macromolecule synthesis and degradation and balance between pumps and leaks. Cation pumps and leaks constitute a major component of energy utilization and are central to other cell functions, even during minimal metabolism. Hence, the maintenance of ion gradients is a central issue in understanding adaptation not only to hypothermia but also to starvation and hypothermia. Of the three hypometabolic states, hypothermia has been best studied in this regard. In most cases, passive permeability is more reduced at low temperature in cold-tolerant cells than in cold-sensitive ones. In some cases there is also a difference in Na-K pump activity and perhaps in ATP dependent Ca-pump activity. Pump activities and probably the maintenance of minimal leak require ongoing metabolism. The question of whether, in cold-sensitive cells, energy supplies are adequate at low temperature was once the focus of this field, but has been ignored for a decade without having been fully resolved. There are many instances of less temperature sensitivity of specific metabolic activities (mitochondrial respiration, etc.) in hibernators than in non-hibernators, without any verification of whether this is essential for survival at low body temperature. Certainly, robust pumping has been found in some failing cold-sensitive cells at low temperature, suggesting no shortage of ATP in these cases, but in other cases the issue may be a more complex one than just that of ATP availability.(ABSTRACT TRUNCATED AT 400 WORDS)