chapter  9
30 Pages

Cellular Calcium Regulation and Signaling

Department of Molecular Biosciences, School of Veterinary Medicine and Center for Environmental Health Sciences, University o f California, Davis, California, USA

Global Calcium Homeostasis: Extracellular Calcium Signaling Calcium as Second Messenger: Intracellular Calcium Signaling • Calcium Transport in Mitochondria • Calcium Regulation in ER/SR Calcium Regulation in Muscle: Excitation Contraction Coupling Calcium Regulation in Neurons: Excitation Response Coupling Ryanodine Receptors • Ryanodine Binding to Conformationally Sensitive Sites on ER/SR Channels • Structure and Tissue Distribution • Accessory Proteins • Immunophilin: FKBP12 FKBP12/RyR Mechanism for Ortho-Substituted PCB Neurotoxicity Acknowledgments References

GLOBAL CALCIUM HOMEOSTASIS: EXTRACELLULAR CALCIUM SIGNALING

In most living cells, both extracellular and intracellular calcium levels ([Ca2+]0 and [Ca2+]i, respectively) are highly regulated, often with the expense of energy. Normally [Ca2+]0 is buffered at approximately 1 to 2 mM (1). In addition to supplying Ca2+ necessary for intracellular signaling and regulation of several cell functions described herein, [Ca2+]0 also plays a role as a first messenger important to the integrity of several structural (e.g., bone matrix) and functional (e.g., blood clotting) processes. The extremely stable [Ca2+]0 level is attributed to homeostatic mechanisms that consist of Ca2+-sensory cells (e.g., parathyroid cells) and Ca2+-responsive tissues (e.g., kidney, bowel, and bone). The “global” [Ca2+]0 balance in a mammal is regulated through concerted changes in disposition, mobilization, and excretion of calcium (in the free and bound forms) by these systems (2-4).