Effect of hyposmotic challenge on microvillous membrane potential in isolated human placental villi.

This study examined the effect of hyposmotic solutions on the syncytiotrophoblast microvillous membrane potential (Em) in mature intermediate villi isolated from term human placentas. When villi were exposed to a control solution (280 mosmol/kgH2O; 116 mM NaCl) and then to either a 138-hyposmotic (138 mosmol/kgH2O; 37 mM NaCl) or 170-hyposmotic (170 mosmol/kgH2O; 55 mM NaCl) solution, there was a significant hyperpolarization of Em (-5.1 +/- 1.5 mV, P < 0.01 and -5.0 +/- 0.5 mV, P < 0.001, respectively; n = 10), which was reversible on removal of the hyposmotic stimulus. Low-NaCl (37 and 55 mM) solutions made isosmotic with control (i.e., 280 mosmol/kgH2O) by addition of raffinose did not significantly alter Em, suggesting that reducing NaCl concentration per se had no effect on Em. Exposure to 170-hyposmotic solution in the presence of 5 mM BaCl2 depolarized Em by +4.1 +/- 0.7 mV (P < 0.001, n = 6); BaCl2 similarly depolarized Em when added in control solution (+5.6 +/- 1. 1 mV, n = 5). Exposure to 170-hyposmotic solution containing 1 mM DIDS hyperpolarized Em by -9.0 +/- 1.7 mV (P < 0.001, n = 5). This degree of hyperpolarization was significantly greater than that observed in hyposmotic solution alone (P < 0.01) but was not different from the hyperpolarization when DIDS was added to control solution (-7.4 +/- 0.2 mV, n = 6). We conclude 1) that Ba2+-sensitive K+ conductances and DIDS-sensitive anion conductances contribute to the resting potential of the syncytiotrophoblast microvillous membrane and 2) that the syncytiotrophoblast microvillous membrane responds to a hyposmotic stimulus by activating both Ba2+-sensitive K+ and DIDS-sensitive anion conductances.

Microvillous membrane potential (Em) in villi from first trimester human placenta: comparison to Em at term.

The microvillous membrane (MVM) potential (Em) of first trimester human placental villi was measured and compared with that in villi from term human placentas. The median Em in first trimester villi (-28 mV) was significantly more negative than that at term (-21 mV; P < 0.001). The median Em measured in villi from early (weeks 6-11) first trimester (-32 mV) was significantly more negative than that in late (weeks 12 and 13) first trimester villi (-24 mV; P < 0.001). Elevating extracellular KCl concentration induced a significant depolarization of Em in both first trimester and term villi (P < 0.05 and P < 0.001, respectively). The magnitude of this depolarization was greater in first trimester than at term, indicating that the ion conductance of the MVM changes with gestation. Exposure to ouabain induced a significant depolarization of Em (3 mV: P < 0.05) in first trimester villi but had little effect at term. These results suggest that microvillous membrane electrophysiology changes with placental development. An alteration in the relative K+:Cl- conductance of the MVM is likely to be a major contributor to the change in the magnitude of Em.

The effect of diabetes mellitus on urinary calcium excretion in pregnant rats and their offspring.

The effect of maternal diabetes mellitus on renal calcium excretion in pregnant rats and their offspring has been examined in order to ascertain the role of the kidney in the disturbed calcium homeostasis of infants born to diabetic mothers. Diabetic pregnant (DP) rats exhibited severe hypercalciuria which greatly exceeded the urinary calcium losses (UCaV) in non-diabetic pregnant (CP) or non-pregnant diabetic (D) rats. Means +/- S.E.M. for UCaV at day 21 (mmol/24 h) were: DP = 1.12 +/- 0.09 (n = 7); CP = 0.06 +/- 0.01 (n = 7); D = 0.63 +/- 0.06 (n = 7) (P < 0.001 DP vs CP and DP vs D). The profile for urinary calcium excretion in the three groups was different from that of other measured ions. The degree of natriuresis, for example, was comparable in DP and D rats at all stages studied. Although magnesium output was significantly greater in DP than D rats on days 14 and 21, this appeared to result from an additive effect of the magnesiuresis seen when pregnancy and diabetes were studied separately. The marked renal calcium wasting of diabetic pregnancy will have implications for overall calcium balance in the mother. For example, an enhanced intestinal calcium absorption was seen in DP rats in the second half of gestation. Means +/- S.E.M. for day 21 (mmol/24 h) were: DP = 3.8 +/- 0.8 (n = 7); CP = 1.4 +/- 0.3 (n = 7); D = 1.6 +/- 0.3 (n = 7) (P < 0.05 DP vs CP and DP vs D).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of diabetes mellitus on maternofetal flux of calcium and magnesium and calbindin9K mRNA expression in rat placenta.

The effect of maternal diabetes mellitus on placental unidirectional maternofetal flux of calcium (Ca) and magnesium (Mg), calbindin9K mRNA expression, and net fetal Ca and Mg accretion has been investigated using control (C), untreated diabetic (D(O)) and insulin-treated diabetic (DI) rats. Unidirectional maternofetal flux of Ca in the D(O) group was 61 and 63% of the value of the C and DI groups; unidirectional maternofetal flux of magnesium in the D(O) group was 79 and 66% of the value in the C and DI groups. Fetal Ca and Mg content (mmol; mean +/- SEM) was also significantly lower in the D(O) group compared with the other two groups (0.111 +/- 0.004 versus 0.153 +/- 0.008 in C and 0.168 +/- 0.007 in DI, p < 0.01 D(O) versus C and DI for Ca; and 0.021 +/- 0.001 versus 0.027 +/- 0.001 in C and 0.031 +/- 0.001 in DI, p < 0.01 D(O) versus C and DI for Mg). However, only Ca content was significantly lower in the D(O) group when normalized to fetal ash weight. Densitometric analysis of autoradiograms after Northern hybridization with cDNA probes demonstrated that the placental calbindin9K/cyclophilin mRNA ratio was 11- to 12-fold lower in the D(O) group compared with the C and DI groups. Collectively, the data suggest that untreated maternal diabetes mellitus reduces fetal Ca and Mg accretion by an effect on the expression of placental transport components involved in the maternofetal transfer of these cations.

Effects of gentamicin, neomycin and tobramycin on renal calcium and magnesium handling in two rat strains.

1. Standard renal clearance techniques were used to compare the acute effects of gentamicin, neomycin and tobramycin on renal calcium and magnesium handling in Sprague-Dawley and Fischer 344 rats. 2. Significant hypercalciuric and hypermagnesiuric responses to all three drugs (P < 0.01) were apparent within 30 min of the onset of drug infusion. 3. The magnitude of the acute hypercalciuric and hypermagnesiuric response to the three aminoglycosides was comparable. This contrasts with their nephrotoxic action where neomycin >> gentamicin > tobramycin. The magnitude of the acute physiological responses to these drugs do not therefore reflect their nephrotoxic potential. 4. Sprague-Dawley rats were at least as responsive as Fischer rats in their acute renal responses to gentamicin. If Fischer rats are more sensitive to aminoglycoside nephrotoxicity than Sprague-Dawley rats, this is not reflected in their acute responses to gentamicin.