Calcium resting cell concentration

In the cytosol of muscle cells, the free Ca " ranges from 10 M (resting cells) to more than 10 (contracting cells), whereas the total Ca concentration In the SR lumen can be as high as 10 M. However, two soluble proteins In the lumen of SR vesicles bind Ca " and serve as a reservoir for intracellular Ca ", thereby reducing the concentration of free Ca " ions In the SR vesicles and conse-quendy the energy needed to pump Ca " ions into them from the cytosol. The activity of the muscle Ca " ATPase increases as the free Ca " concentration in the cytosol rises. Thus in skeletal muscle cells, the calcium pump in the SR membrane can supplement the activity of a similar Ca " pump located in the plasma membrane to assure that the cytosolic concentration of free Ca " in resting muscle remains below 1 jjlM. 

The total concentration of calcium in the blood plasma is ca. 2 mM, and about half of it is bound to proteins, mainly serum albumin. This high calcium concentration is typical for all extracellular fluids, in stark contrast to the very low free calcium concentration in resting cells. One might therefore be led to believe that there is no specific function of calcium in the extracellular fluids. This is certainly not true. It has been known for almost a century that calcium is critical for blood coagulation, and it is also well known that calcium is a major component in our skeleton. It is, however, also obvious that the requirement for a protein to be calcium binding in a milieu with free calcium at 1 mM is very different from one with calcium at p.M levels. 

The Ca(Il) coaceatratioa ia blood is closely coatroUed aormal values He betweea 2.1 and 2.6 mmol/L (8.5—10.4 mg/dL) of semm (21). The free calcium ion concentration is near 1.2 mmol/L the rest is chelated with blood proteias or, to a lesser extent, with citrate. It is the free Ca(Il) ia the semm that determines the calcium balance with the tissues. The mineral phase of bone is essentially ia chemical equiUbrium with calcium and phosphate ions present ia blood semm, and bone cells can easily promote either the deposition or dissolution of the mineral phase by localized changes ia pH or chelating... 

Like Na+, the calcium ion is actively excluded from cells. Indeed, 99% of the calcium in the human body is present in the bones/ 3 The blood serum concentration of Ca2+ is -3 mM, of which 1.5 mM is free. The rest is chelated by proteins, carbohydrates, and other materials. Within cells the concentration of free Ca2+ is < 1 pM and typically -0.05-0.2 pM for unexcited cells. d -f However, the total intracellular Ca2+ is considerably higher and may be in excess of 1 mM. Approximate total concentrations are red blood cells, 20 pM liver, 1.6 mM and heart, 4 mM. 

The cytosol is the cell compartment in which most mechanisms of Ca2+ signalling converge to produce the specific spatial-temporal pattern of the signal appropriate for targeting its effectors. The resting concentration of calcium in the cytosol is low,... 

Calcium performs a variety of cellular functions in muscle and nerve that ultimately result in muscular contraction. Excellent descriptions of calcium s function in muscle and nerve are to be found in the reviews by Hoyle (37), Cohen (38), and Robertson (39). At the neuromuscular junction, the excitable cells are very sensitive to changes in extracellular concentrations of calcium. Curtis (40) and Luttgau (41) described a fall in the resting action potential and electrical resistance when the extracellular calcium concentration fell below 10 M. The action potential and electrical resistance returned to normal following addition of calcium to this vitro preparation. The magnitude of the Initial muscle membrane action potential, that which regulates the propagation of further muscle contraction, is also mediated by the extracellular calcium concentration. While the inward flow of sodium ions from the extracellular space remains the dominant factor in the mechanism of muscle membrane depolarization, calcium ion flux appears to mediate the cell s permeability to sodium ions. This effect is particularly true in cardiac tissue (W). 

Figure 6.1. Overview of cellular calcium transport. Calcium enters the cell through voltage- or ligand-gated channels (left). It is extmded by ATP-driven pumps or by sodium antiport (right). Both the mitochondria and the endoplasmic reticulum serve as intracellular calcium stores. The cytosolic concentration is kept at -100 nM under resting conditions. CaM Calmodulin.

Inositol trisphosphate opens a calcium transport channel in the membrane of the endoplasmic reticulum. This leads to an influx of calcium from storage in the endoplasmic reticulum and a 10-fold increase in the cytosolic concentration of calcium ions. Calmodulin is a small calcium binding protein found in all cells. Its affinity for calcium is such that, at the resting concentration of calcium in the cytosol (of the order of 0.1 /xmol per L), little or none is bound to calmodulin. When the cytosolic concentration of calcium rises to about 1 /xmol per L, as occurs in response to opening of the endoplasmic reticulum calcium transport channel, calmodulin binds 4 mol of calcium per mol of protein. When this occurs, calmodulin undergoes a conformational change, and calcium-calmodulin binds to, and activates, cytosolic protein kinases, which in turn phosphorylate target enzymes. 

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