Adaptive mechanisms of intracellular calcium homeostasis in mammalian hibernators

Abstract

SUMMARYIntracellular Ca2+ homeostasis is a prerequisite for a healthy cell life. While cells from some mammals may suffer dysregulation of intracellular Ca2+ levels under certain deleterious and stressful conditions, including hypothermia and ischemia, cells from mammalian hibernators exhibit a remarkable ability to maintain a homeostatic intracellular Ca2+ environment. Compared with cells from non-hibernators, hibernator cells are characterized by downregulation of the activity of Ca2+ channels in the cell membrane, which helps to prevent excessive Ca2+ entry. Concomitantly, sequestration of Ca2+ by intracellular Ca2+ stores, especially the sarcoplasmic/endoplasmic reticulum, is enhanced to keep the resting levels of intracellular Ca2+ stable. An increase in stored Ca2+ in heart cells during hibernation ensures that the levels of Ca2+messenger are sufficient for forceful cell contraction under conditions of hypothermia. Maintenance of Na+ gradients, viaNa+—Ca2+ exchangers, is also important in the Ca2+ homeostasis of hibernator cells. Understanding the adaptive mechanisms of Ca2+ regulation in hibernating mammals may suggest new strategies to protect nonhibernator cells, including those of humans, from Ca2+-induced dysfunction.