Related Experiment Videos
Intracellular calcium signalling and vascular reactivity in Bartter's syndrome
L Calò1, A D'Angelo, S Cantaro
1Department of Internal Medicine, University of Padova, Italy.
Abstract:
We investigated patients affected by Bartter's syndrome in the attempt to localize the intracellular defect mediating the reduced intracellular Ca2+ mobilization that may be responsible for the decreased vascular reactivity characteristic of Bartter's syndrome. Using the formylmethionyl-leucyl-phenylalanine (fMLP) receptor system, which causes, intracellular calcium release, we investigated fMLP-stimulated intracellular inositol 1,4,5-trisphosphate (IP3) production as well as the number and affinity of fMLP receptors in neutrophils from Bartter's syndrome patients and healthy controls. Scatchard plot analysis of radioactive fMLP binding to neutrophils indicated that there were no differences in either cell receptor number and affinity for ligand between healthy controls (n = 5) and patients with Bartter's syndrome (n = 5): 6,151 +/- 1,431 vs. 7,112 +/- 2,566 receptors/cell; K(D): 0.446 +/- 0.14 vs. 0.454 +/- 0.09 pM of fMLP. 5- and 10-second fMLP-stimulated intracellular IP3 production was instead reduced in patients affected by Bartter's syndrome: 2.479 +/- 1.07 vs. 4.073 +/- 1.04 nmol/10(7) cells at 5 s (n = 8; p < 0.01); 1.673 +/- 0.741 vs. 3.766 +/- 1.348 nmol/10(7) cells at 10 s (n = 8; p < 0.005). The results of this study indicate that the anomaly of intracellular calcium mobilization in patients with Bartter's syndrome arises from a defect at the postreceptor level. The anomalous calcium signalling that takes place in Bartter's syndrome may provide a mechanism for the hyporesponsiveness to pressor stimuli characteristic of these patients.
Insights
Patients with Bartter's syndrome show reduced intracellular calcium signaling due to a post-receptor defect. This calcium anomaly may explain their decreased vascular reactivity and hyporesponsiveness to stimuli.
Area of Science:
- Biochemistry
- Physiology
- Pathology
Background:
- Bartter's syndrome is characterized by reduced vascular reactivity, potentially linked to impaired intracellular calcium mobilization.
- Understanding the cellular defect in calcium signaling is crucial for explaining Bartter's syndrome pathophysiology.
Purpose of the Study:
- To investigate the intracellular defect responsible for reduced calcium mobilization in Bartter's syndrome.
- To compare formylmethionyl-leucyl-phenylalanine (fMLP) receptor function and calcium signaling in Bartter's syndrome patients versus healthy controls.
Main Methods:
- Neutrophils from Bartter's syndrome patients and controls were used to assess fMLP receptor binding and fMLP-stimulated inositol 1,4,5-trisphosphate (IP3) production.
- Scatchard plot analysis determined the number and affinity of fMLP receptors.
- Intracellular IP3 production was measured at 5 and 10 seconds post-fMLP stimulation.
Main Results:
- No significant differences were found in the number or affinity of fMLP receptors between Bartter's syndrome patients and healthy controls.
- fMLP-stimulated intracellular IP3 production was significantly reduced in Bartter's syndrome patients at both 5 and 10 seconds.
- This indicates a defect in calcium mobilization at the post-receptor level.
Conclusions:
- The impaired intracellular calcium mobilization in Bartter's syndrome originates from a post-receptor defect.
- This anomalous calcium signaling may underlie the characteristic hyporesponsiveness to pressor stimuli observed in Bartter's syndrome.