Calcium release

Saito, A., et al., 1988. Ultrastrnctnre of die calcium release channel of sarcoplasmic redcnlnm. of Cell Biology 107 211-219. 

Calcium channels in the plasma membrane activated after receptor-mediated calcium release from intracellular stores. Diese channels are present in many cellular types and play pivotal roles in a multitude of cell functions. It was recently shown that Orai proteins are the pore-forming subunit of CRAC channels. They are activated by STIM proteins that sense the Ca2+ content of the endoplasmic reticulum. 

IP3 receptor associated cGMP kinase substrate of 130 kDa that is present in all smooth muscles and platelets. It s phosphorylation decreases calcium release from intracellular EP3-sensitive stores. 

The NHR contains also the conserved Calcineurin docking site, PxlxIT, required for the physical interaction of NEAT and Calcineurin. Dephosphorylation of at least 13 serines residues in the NHR induces a conformational change that exposes the nuclear localization sequences (NLS), allowing the nuclear translocation of NEAT. Rephosphorylation of these residues unmasks the nuclear export sequences that direct transport back to the cytoplasm. Engagement of receptors such as the antigen receptors in T and B cells is coupled to phospholipase C activation and subsequent production of inositol triphosphate. Increased levels of inositol triphosphate lead to the initial release of intracellular stores of calcium. This early increase of calcium induces opening of the plasma membrane calcium-released-activated-calcium (CRAC) channels,... 

Fill M, Copello JA (2002) Ryanodine receptor calcium release channels. Physiol Rev 82 893-922... 

Wehrens XH, Lehnart SE, Marks AR (2005) Intracellular calcium release and cardiac disease. Annu Rev Physiol 67 69-98... 

However, the total regulatory system is not so simple and linear. In skinned muscle preparations especially, it can be shown that there are calcium stores which cannot be released by IP3 but which are released by elevated levels of calcium itself That is, by the mechanism of calcium induced calcium release (CICR). The CICR... 

Smith, J.S., Coronado, R., Meissner, G. (1986). Single channel measurements of the calcium release charmel from skeletal muscle sarcoplasmic reticulum. J. Gen. Physiol. 88, 573-588. 

Dantrolene is the mainstay of MH treatment. It has long been available for the treatment of muscle spasm in cerebral palsy and similar diseases. It is a hydantoin derivative that was first synthesized in 1967, and reported to be effective in the treatment of porcine MH in 1975. Also in 1975, dantrolene was shown to be more effective than procainamide in the treatment of human MH, which until that time was the drug of choice. However, the intravenous preparation was not made available until November 1979. It significantly lowered mortality. The half-life of dantrolene is estimated to be 6-8 hr. Dantrolene s primary mode of action is the reduction in calcium release by the sarcoplasmic reticulum. Dantrolene also exerts a primary antiarrhythmic effect by increasing atrial and ventricular refractory periods. Side effects of dentrolene include hepatotoxicity, muscle weakness, ataxia, blurred vision, slurred speech, nausea, and vomiting. Dantrolene is not contraindicated in pregnancy, but it does cross into breast milk and its effect on the neonate is unknown. 

CTC, used extensively to monitor calcium release in both whole cells and isolated organelles (28-33), is an amphipathic molecule that easily passes through cell membranes (see Figure 1). The fluorescence of this probe is enhanced more than fiftyfold by binding of calcium when the dye is intercalated into biological membranes. 

Vig M, DeHaven WI, Bird GS, Billingsley JM, Wang H, Rao PE, Hutchings AB, Jouvin MH, Putney JW, Kinet JP Defective mast cell effector functions in mice lacking the CRACMl pore subunit of store-operated calcium release-activated calcium channels. Nat Immunol 2008 9 89-96. 

Calcium release from mitochondria is facilitated by exchange with Na". ... 

Reactive oxygen species modify the structure and function of the cardiac sarcoplasmic reticulum calcium release channel. Cardioscience 2, 19-25. 

Shattock, M.J., Matsuura, H. and Hearse, D.J. (1991). Functional and electrophysiolc cal effects of oxidant stress on isolated ventricular muscle role for oscillatory calcium release from sarcoplasmic reticulum in arrhythmogenesis. Cardiovasc. Res. 25, 645-651. 

Trimm, J.L., Salama, G. and Abramson, J.J. (1986). Sulphydryl oxidation induces rapid calcium release from sarcoplasmic reticulum vesicles. J. Biol. Chem. 261, 16092-16098. 

For over three decades, laboratory research has shown caffeine to be effective at mobilizing calcium in skeletal muscle. In vitro experiments have amply demonstrated that caffeine lowers the excitability threshold and extends the length of muscular contractions via calcium release from the sarcoplasmic reticulum.1012 Caffeine also inhibits calcium reuptake by the sarcoplasmic reticulum, perpetuating calcium availability for muscle work.1318 Also, caffeine promotes increased twitch tension development in muscles.1718... 

Endo, M., Calcium release from the sarcoplasmic reticulum, Physiology Review, 57, 71, 1977. 

Fabiato, A. and Fabiato, F., Calcium release from sarcoplasmic reticulum, Circ Research, 40, 119, 1977. 

McGrath J, Solter D 1984 Inability of mouse blastomere nuclei transferred to enucleated zygotes to support development invitro. Science 226 1317-1319 Miyazaki S 1988 Inositol 1,4,5-trisphosphate-induced calcium release and guanine nucleotidebinding protein-mediated periodic calcium rises in golden hamster eggs. J Cell Biol 106 345-353... 

Pothoulakis C, Sullivan R, Malnick DA, Triad-afilopoulos G, Gadenne AS, Meshulam T, La-Mont JT Clostridium difficile toxin A stimulates intracellular calcium release and chemo-tactic response in human granulocytes. J Clin Invest 1988 81 1741-1745. 

In addition to the well-known iron effects on peroxidative processes, there are also other mechanisms of iron-initiated free radical damage, one of them, the effect of iron ions on calcium metabolism. It has been shown that an increase in free cytosolic calcium may affect cellular redox balance. Stoyanovsky and Cederbaum [174] showed that in the presence of NADPH or ascorbic acid iron ions induced calcium release from liver microsomes. Calcium release occurred only under aerobic conditions and was inhibited by antioxidants Trolox C, glutathione, and ascorbate. It was suggested that the activation of calcium releasing channels by the redox cycling of iron ions may be an important factor in the stimulation of various hepatic disorders in humans with iron overload. 

The functions of mtNOS in mitochondria have been studied (see Chapter 23). Ghafourifar et al. [177] found that the calcium-induced stimulation of mtNOS caused the release of cytochrome c from mitochondria and induced apoptosis. On the other hand, the same group of authors [178] showed that the production of NO by mtNOS and superoxide in mitochondria resulted in the formation of peroxynitrite and stimulated calcium release, indicating the existence of a feedback loop which prevents calcium overload in mitochondria. 

Cox, D. A. and Cohen, M. L. 5-HT2B receptor signaling in the rat stomach fundus dependence on calcium influx, calcium release and protein kinase C. Behav. Brain Res. 73 289-292,1996. 

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