The Mechanism Enabling Hibernation in Mammals.

Abstract

Some rodents including squirrels and hamsters undergo hibernation. During hibernation, body temperature drops to only a few degrees above ambient temperature. The suppression of whole-body energy expenditure is associated with regulated, but not passive, reduction of cellular metabolism. The heart retains the ability to beat constantly, although body temperature drops to less than 10°C during hibernation. Cardiac myocytes of hibernating mammals are characterized by reduced Ca2+ entry into the cell membrane and a concomitant enhancement of Ca2+ release from and reuptake by the sarcoplasmic reticulum. These adaptive changes would help in preventing excessive Ca2+ entry and its overload and in maintaining the resting levels of intracellular Ca2+. Adaptive changes in gene expression in the heart prior to hibernation may be indispensable for acquiring cold resistance. In addition, protective effects of cold-shock proteins are thought to have an important role. We recently reported the unique expression pattern of cold-inducible RNA-binding protein (CIRP) in the hearts of hibernating hamsters. The CIRP mRNA is constitutively expressed in the heart of a nonhibernating euthermic hamster with several different forms probably due to alternative splicing. The short product contained the complete open reading frame for full-length CIRP, while the long product had inserted sequences containing a stop codon, suggesting production of a C-terminal deletion isoform of CIRP. In contrast to nonhibernating hamsters, only the short product was found in hibernating animals. Thus, these results indicate that CIRP expression in the hamster heart is regulated at the level of alternative splicing, which would permit a rapid increment of functional CIRP when entering hibernation. We will summarize the current understanding of the cold-resistant property of the heart in hibernating animals.