Mechanisms of metabolic defense against hypoxia in hibernating frogs

The cold submerged frog (Rana temporaria) serves as a useful model for many hibernating ectotherms that take refuge in hypoxic ponds and lakes until more favourable conditions of climate and food availability return. In all such animals, entry into a hypometabolic state effectively extends their survival time by lessening the impact of ATP demands on endogenous substrates. At the cellular level, metabolic depression may be brought about by decreasing energy-consuming processes and/or by increasing the efficiency of energy-producing pathways. Since the mitochondrion is the major contributor to the total energy production during aerobic metabolism and frog survival during winter depends on entry into a hypometabolic state, this review focuses on the respiratory properties of mitochondria that serve to increase the efficiency of energy production in hibernation. Energy conservation during overwintering also occurs through decreases in the ATP demand of the energy-consuming processes. For example, hibernating frogs decrease their ATP demands for Na⁺/K⁺-ATPase activity as part of a coordinated process of energy conservation wherein O₂-limitation initiates a generalised suppression of ion channel densities and/or channel leak activities. The net result is that cell membrane permeabilities are reduced, thereby lowering the energetic costs of maintaining transmembrane ion gradients.