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      Mechanisms of Renal Calcium Transport

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          The kidneys play a key role in the integrated regulation of calcium homeostasis. Calcium absorption takes place throughout the nephron. Proximal tubules, thick ascending limbs of Henle’s loop, and distal tubules are the major sites of calcium absorption. The mechanisms of absorption vary significantly from one segment to another, as does the extent of hormonal regulation. At one extreme is the considerable reabsorption by proximal tubules that proceeds primarily, if not entirely, by a paracellular pathway that is not regulated by hormones or drugs. In thick ascending limbs, calcium absorption occurs through a combination of transcellular and paracellular routes. The active, transcellular component is regulated by parathyroid hormone (PTH) and calcitonin, whereas the passive, paracellular route is governed by the extent of concomitant sodium absorption. At the other extreme is the distal tubule, where calcium absorption is entirely transcellular and is regulated by PTH, 1,25(OH)<sub>2</sub>vitamin D<sub>3</sub>, calcitonin, and by calcium-sparing drugs such as thiazide-type diuretics. The present review focuses on recent insights into the mechanisms of transcellular calcium movement and highlights the discovery of an epithelial calcium channel, ECaC, that may mediate calcium entry in distal tubules.

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          Most cited references 9

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          Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK.

          Mutations in the Na-K-2Cl cotransporter (NKCC2), a mediator of renal salt reabsorption, cause Bartter's syndrome, featuring salt wasting, hypokalaemic alkalosis, hypercalciuria and low blood pressure. NKCC2 mutations can be excluded in some Bartter's kindreds, prompting examination of regulators of cotransporter activity. One regulator is believed to be ROMK, an ATP-sensitive K+ channel that 'recycles' reabsorbed K+ back to the tubule lumen. Examination of the ROMK gene reveals mutations that co-segregate with the disease and disrupt ROMK function in four Bartter's kindreds. Our findings establish the genetic heterogeneity of Bartter's syndrome, and demonstrate the physiologic role of ROMK in vivo.
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            Cloning and expression of an inwardly rectifying ATP-regulated potassium channel.

            A complementary DNA encoding an ATP-regulated potassium channel has been isolated by expression cloning from rat kidney. The predicted 45K protein, which features two potential membrane-spanning helices and a proposed ATP-binding domain, represents a major departure from the basic structural design characteristic of voltage-gated and second messenger-gated ion channels. But the presence of an H5 region, which is likely to form the ion conduction pathway, indicates that the protein may share a common origin with voltage-gated potassium channel proteins.
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              Neural basis of saccade target selection in frontal eye field during visual search.

              Conspicuous visual features commonly attract gaze, but how the brain selects targets for eye movements is not known. We investigated target selection in rhesus monkeys performing a visual search task by recording neurons in the frontal eye field, an area known to be responsible for generating purposive eye movements. Neurons with combined visual- and eye movement-related activity were analysed. We found that the initial visual responses to search stimulus arrays were the same whether the target or a distractor was in the response field. We also found that the neural activity evolved to specify target location before the execution of eye movements, ultimately peaking when the target was in the response field and being suppressed when the target was beside but not distant from the response field. These results demonstrate a possible mechanism by which a desired target is fixated and inappropriate eye movements are prevented.

                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                December 2000
                15 September 2000
                : 8
                : 6
                : 343-350
                Departments of Pharmacology and of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pa., USA
                20688 Exp Nephrol 2000;8:343–350
                © 2000 S. Karger AG, Basel

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                Page count
                Figures: 3, Tables: 1, References: 49, Pages: 8
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