Cytosolic calcium levels

Ionized calcium (Ca2+) is the most common signal transduction element in cells [66], Excitable cells, like neurons, contain voltage-dependent Ca2+ channels, which enable these cells to drastically increase cytosolic calcium levels. Rapid fluctuations in presynaptic... 

Increases in the concentration of calcium in the cytosol provides a signal that can initiate muscle contraction, vision, and other signaling pathways. The response depends on the cell type. In muscle, a transient rise in the cytosolic calcium levels (from opening calcium channels in the sarcoplasmic reticulum) causes contraction. This signaling in contraction is a direct consequence of electrical activation of the voltage-gated channel. 

Calcium signaling is also involved in the response to growth factors. Normally, cells maintain low calcium levels in the cytosol. A low cytosolic calcium level is maintained by pumps that use ATP hydrolysis to move Ca2+ out of the cytosol. Ca2+ concentration in the cytosol increases by activating a calcium channel that lets Ca2+ flow back into the cytosol. 

The exact mechanisms by which BDNF enhances the induction of LTP remain obscure. Nevertheless, both pre-and postsynaptic mechanisms appear to be possible. As mentioned above, BDNF elevates presynaptic cytosolic calcium level and thus increases vesicular neurotransmitter release. When a postsynaptic neuron is injected with a Trk tyrosine kinase inhibitor (K252a), BDNF-augmented LTP is curtailed this suggests that a postsynaptic mechanism is adopted by BDNF in the manifestation of LTP. It has been postulated that neurotrophins may act as... 

Vascular tone is regulated by the cytosolic calcium level, the interaction of calcium and calmodulin with myosin light-chain kinase, and subsequent myosin light-chain phosphorylation, which promotes the interaction of myosin with actin and finally leads to contraction. 

Removal of free cytosolic calcium If free cytosolic calcium levels were to remain high, the cardiac muscle would be in a constant state of contraction, rather than showing a periodic contraction. Mechanisms of removal include two alternatives. 

Johnson, J.D., Conroy, W.G., Isom, G.E. (1987). Alteration of cytosolic calcium levels in PC12 cells by potassium cyanide. Toxicol. Appl. Pharmacol. 88 217-24. 

We will consider the structural and mechanistic features of these enzymes by examining the Ca2+ ATPase found in the sarcoplasmic reticulum (SR Ca2+ ATPase) of muscle cells. This enzyme, which constitutes 80% of the sarcoplasmic reticulum membrane protein, plays an important role in muscle contraction, which is triggered by an abrupt rise in the cytosolic calcium level. Muscle relaxation depends on the rapid removal of Ca + from the cytosol into the sarcoplasmic reticulum, a specialized compartment for calcium storage, by the SR Ca + ATPase. This pump maintains a Ca2+ concentration of approximately 0.1 iM in the cytosol compared with 1.5 mM in the sarcoplasmic reticulum. 

J.l Cytosolic calcium levels and platelet reactivity in hypertension... 

Epinephrine in both skeletal muscle and heart affects both a-1 and b-receptors. The major effect on the a-1 receptors is an increase of inositol trisphosphate (IP 3), causing an increase in cytosolic calcium levels both from intracellular sources, such as sarcoplasmic reticulum, T-tubules, and so on, and from opening some calcium... 

The excessive production of such radicals will initiate a cascade of oxidation-reduction reactions (oxidative stress) that finally may lead to the loss of cellular integrity. The causes of injury considered include increased cytosolic calcium levels, ATP depletion, thiol oxidation, lipid peroxidation, DNA damage and critical damage to the organelles - that is, the mitochondria and lysosomes. 

Endothelin-1 (ET-1) is a 21-amino-acid peptide that is produced by the vascular endothelium. It is a very potent vasoconstrictor that binds to VSM endothelin receptors ETa and ETB(Fig. 29.1). The ET-1 receptors are linked to the Gq protein and IP3 signal transduction pathway (Fig. 29.11). Therefore, ET-1 causes sarcoplasmic reticulum release of calcium, increasing the VSM contractility. Vascular endothelial cells secrete the majority of ET-1. The endothelins bind to two receptor subtypes ETa, and ETb. Invasculartissue, ETa is located predominantly on smooth muscle cells, whereas ETb is found on both endothelial and smooth muscle cells. Activation of ETa by ET-1 leads to potent vasoconstriction from an increase in cytosolic calcium levels via influx of extracellular calcium and release from intracellular stores (Fig. 29.1). The actions of ETb are more complicated. Like ETa, ET-1 activation of ETb on VSM cells leads to vasoconstriction. Furthermore, some studies suggest that in the pulmonary hypertensive state, blockade of both ETa and ETb is necessary to achieve maximal vasodilation. Activation of ET-B by ... 

De la Rosa, L.A., Alfonso, A., Vilarino, N., Vieytes, M.R., and Botana, L.M., Modulation of cytosolic calcium levels of human lymphocytes by yessotoxin, a novel marine phycotoxin, Biochem. Pharmacol., 61, 827, 2001. 

FIGURE 14.1 Effects of YTX on cytosolic calcium levels in human lymphocytes... 

In a similar model, AZA-4 was reported not to modify cytosolic calcium in resting human lymphocytes. However, AZA-4 inhibited the increase in cytosolic calcium levels induced by Tg in a dose-dependent manner but did not affect the Ca -release from internal stores induced by this drug. These effects were reversible and not regulated by cAMP pathway. AZA-4 appeared to be a novel inhibitor of plasma membrane Ca channels, affecting store-operated channels, showing an effect different from other AZA analogues.It was the author s opinion that the inability of AZA-4 and AZA-5 to increase Ca influx lowered their relative toxicity compared to AZA-1 and AZA-3. 

---