Biological discrimination between calcium and strontium in kidneys and bone of young and adult rats

Effects of aging on the biological discrimination between calcium (Ca) and strontium (Sr) by the kidneys and bone were studied in male and female rats of 5 to 50 wk of age by examining Sr/Ca ratios in the plasma, urine, and bone. The Ca-Sr discrimination at the reabsorption process in the kidneys was not affected by aging in male or female rats. On the other hand, discrimination between the two elements was shown to be age-related at the absorption process in the digestive tract, and became more strict with age. The reverse situation was observed in the discrimination of Ca and Sr in the femur; younger rats discriminated the two elements more strictly than older animals.     

Discrimination between strontium and calcium in suckling rats

Discrimination between strontium (Sr) and calcium (Ca) was examined in suckling rats and compared with that in older rats after weaning. Concentrations of Sr and Ca and the Sr/Ca ratios in serum and femur of 10-d old and 21-d old rats were determined. The Sr concentrations and Sr/Ca ratios in the serum and femur of 10-d old rats were lower than those of 21-d old rats, that could be explained by the fact that 10-d old rats ingested only maternal milk in which the Sr/Ca ratio was much lower than the laboratory diet. The relative ratios of Sr/Ca in serum and femur to that in the diet were found to be higher in 10-d old rats compared with those in 21-d old rats, and also higher than those in the older rats after weaning, as described in our previous publication. This result may reflect that discrimination between Sr and Ca during intestinal absorption is lacking in very young animals before weaning and develops after this age. Renal discrimination between Sr and Ca in the suckling rats at 10 d of age was evaluated by determining the relationship between the relative clearances of Ca and Sr. The mathematical model proposed by Walser and Robinson was applied on these results and the parameter for the equation, that is, the discrimination constant, was shown to be higher in 10-d old rats compared to those in young (7 wk of age) and adult (25 wk of age) rats. This result suggests that the discrimination of Sr in favor of Ca during the tubular reabsorptive process may not be fully developed in the very young rats before weaning.     

Comparison between strontium and calcium uptake by the fragmented sarcoplasmic reticulum.

The ATP-supported uptake of strontium by the fragmented sarcoplasmic reticulum is monophasic and proceeds more rapidly than the fast uptake of calcium. Strontium uptake is not activated by Pi. The accumulation of strontium is nearly proportional to the external strontium concentration even in the millimolar range. Internal and external strontium quickly equilibrate. One mole of strontium is stored for every mole of ATP split by the Sr2+-activated ATPase. In the absence of oxalate most of the strontium is taken up with a transport ratio of one. On the opposite, the transport ratio of calcium decreases immediately, especially when ADP is not instantaneously phosphorylated to ATP. In this case, energy conversion is uncoupled more effectively by the simultaneous action of ADP and free internal calcium, resulting in the interruption of the fast uptake. After depletion of ATP most of the stored strontium is released and the remaining fraction appears to be not exchangeable. Strontium activates the slow uptake of calcium, but reduces the amplitude of the fast uptake. The calcium induced release of strontium, and vice versa, is partial and transient. The strontium activated ATPase does not transport calcium at low ionic calcium concentrations.     

Coupling of strontium and calcium cycles in Lake Constance

The contents of Sr and Ca were measured weekly in Lake Constance in 1986. Epilimnetic concentrations of Ca changed between 1.30 × 10^-3 mol l^-1 (during homothermy) and 0.9 × 10 -3 mol l^-1 (during thermal stratification). The seasonal fluctuations of Ca were correlated with those of Sr (between 4.61 and 5.36 mol l^-1). The epilimnion was permanently oversaturated with respect to calcite but not with respect to SrCO₃. Analysis of the settling process by use of sedimentation traps revealed two short episodes of very high authigenic settling fluxes of CaCO₃, triggered by phytoplankton diatoms. Seasonal changes of the Ca contents (between 4.1 and 30.7 percent of the dry weight) and of the Sr concentrations (from 12 to 75 × 10^-3 percent) in the settling material were closely correlated. This suggests a coprecipitation mechanism with a nearly constant stoichiometry of (atoms Sr/atoms Ca) × 1000 of 0.84. Coprecipitation of Sr or Ca with organic matter was insignificant. In the hypolimnion some Sr and Ca were released from the settling material. These results strongly suggest that the cycle of Sr in Lake Constance is driven predominantly by coprecipitation with calcite. The principal chemical mechanisms leading to coprecipitation are discussed.     

Potassium channel block by internal calcium and strontium

We show that intracellular Ca blocks current flow through open K channels in squid giant fiber lobe neurons. The block has similarities to internal Sr block of K channels in squid axons, which we have reexamined. Both ions must cross a high energy barrier to enter the blocking site from the inside, and block occurs only with millimolar concentrations and with strong depolarization. With Sr (axon) or Ca (neuron) inside, IK is normal in time course for voltages less than about +50 mV; but for large steps, above +90 mV, there is a rapid time-dependent block or "inactivation." From roughly +70 to +90 mV (depending on concentration) the current has a complex time course that may be related to K accumulation near the membrane's outer surface. Block can be deepened by either increasing the concentration or the voltage. Electrical distance measurements suggest that the blocking ion moves to a site deep in the channel, possibly near the outer end. Block by internal Ca can be prevented by putting 10 mM Rb in the external solution. Recovery from block after a strong depolarization occurs quickly at +30 mV, with a time course that is about the same as that of normal K channel activation at this voltage. 20 mM Mg in neurons had no discernible blocking effect. The experiments raise questions regarding the relation of block to normal channel gating. It is speculated that when the channel is normally closed, the "blocking" site is occupied by a Ca ion that comes from the external medium.     

Effect of strontium and magnesium on blood calcium]

Twenty four male Wistar rats weighing 250 +/- 10 g, in three groups of 8 rats each, were used. Group A was used as control and the content of its drinking water was 6.5 mg/l Ca; 2.4 mg/l Mg. The drinking water of groups B and C was supplemented with 20 mM (SrCl2) and 20 mM (MgCl2), respectively. Once the 20 days of mineral supplementation had passed, arterial blood was extracted by puncture in the abdominal aorta. In the serum obtained after centrifugation, Ca, Mg, Sr and the total proteins (TP) were determined. Afterwards the serum was subjected to ultrafiltration. Concentrations of Ca, Mg and TP were measured in the obtained ultrafiltrates (u), with the above described techniques. The pH was measured before and after the ultrafiltration. The TP decreased significantly both in group B (supplemented with Sr), and in group C (supplement with Mg). Increases in Ca were found in group B and in Mg in group C. The Mg/Ca ratio increased 10% after the supplementation with Mg. At the ultrafiltrate a significant increase in Cau after supplementation with Sr and with Mg was observed. The Mgu/Cau ratio decreased 14% in the group supplemented with Sr and 38% after the supplementation with Mg. In conclusion, the supplementation with Sr (20 mM) in rats increases the Cau and could have the effect of reducing protein synthesis. These facts should be borne in mind when Sr is used for therapeutical purposes.