Characterization of Zn2+ transport in Madin-Darby canine kidney cells

Ducoudret, Olivier; Barbier, Olivier; Tauc, Michel; Fuchs, Marianne; Poujeol, Philippe

doi:10.1016/s0005-2736(03)00052-x

Cited by 8 publications

(5 citation statements)

References 24 publications

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“…5E). In these solutions, elevating cytoplasmic Ca 2ϩ to 30 M allowed an inward current near the presumed resting potential of a renal epithelial cell [Ϫ40 to Ϫ80 mV (13,58,65)]. Given the macroscopic currents (Fig.…”

Section: Resultsmentioning

confidence: 99%

The native TRPP2-dependent channel of murine renal primary cilia

Kleene

2017

American Journal of Physiology-Renal Physiology

133

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Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening monogenic renal disease. ADPKD results from mutations in either of two proteins: polycystin-1 (also known as PC1 or PKD1) or transient receptor potential cation channel, subfamily P, member 2 (TRPP2, also known as polycystin-2, PC2, or PKD2). Each of these proteins is expressed in the primary cilium that extends from many renal epithelial cells. Existing evidence suggests that the cilium can promote renal cystogenesis, while PC1 and TRPP2 counter this cystogenic effect. To better understand the function of TRPP2, we investigated its electrophysiological properties in the native ciliary membrane. We recorded directly from the cilia of mIMCD-3 cells, a murine cell line of renal epithelial origin. In one-third of cilia examined, a large-conductance channel was observed. The channel was not permeable to Cl¯ but conducted cations with permeability ratios P:P:P of 1:0.55:0.14. The single-channel conductance ranged from 97 pS in typical physiological solutions to 189 pS in symmetrical 145 mM KCl. Open probability of the channel was very sensitive to membrane depolarization or increasing cytoplasmic free Ca in the low micromolar range, with the open probability increasing in either case. Knocking out TRPP2 by CRISPR/Cas9 genome editing eliminated the channel current, establishing it as TRPP2 dependent. Possible mechanisms for activating the TRPP2-dependent channel in the renal primary cilium are discussed.

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Section: Resultsmentioning

confidence: 99%

The native TRPP2-dependent channel of murine renal primary cilia

Kleene

2017

American Journal of Physiology-Renal Physiology

133

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“…21) In the experiments using Caco-2 cells 37) or MDCK cells, 38) K m were 42 μM and 18.9 μM, respectively. These values agree with our result using Caco-2 cell (11.7 μM).…”

Section: )mentioning

confidence: 99%

<i>In Vitro</i> Study on the Transport of Zinc across Intestinal Epithelial Cells Using Caco-2 Monolayers and Isolated Rat Intestinal Membranes

Yasuno

Okamoto

Nagai

et al. 2012

Biological & Pharmaceutical Bulletin

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The variety of physiologic and biologic functions of zinc is fascinating and could be applicable to medicine. Our previous studies demonstrated that the absorption of zinc after oral administration to rats is dose-dependent. In order to clarify the detailed mechanism of the dose-dependent in vivo absorption, the transport of zinc across intestinal epithelial cells was investigated using Caco-2 monolayers and isolated rat intestinal membranes. The permeation of zinc across Caco-2 monolayers is concentration-dependent, and both saturable and nonsaturable components are involved. The Michaelis constant and maximum transport rate for saturable transport are 11.7 μM and 31.8 pmol min 1 cm 2 , respectively; the permeability coefficient for nonsaturable trasnport is 2.37 10 6 cm s 1 . These parameters for permeation across membranes isolated from duodenum, ileum, and jejunum of rats are similar with those of Caco-2 cells. The comparison of the parameters for permeation across isolated intestinal membrane suggests that the major site of intestinal zinc absorption in rats is the duodenum. The maximum rate of zinc transport across the isolated intestinal membrane (V max ) shows no correlation with mRNA expression of ZIP4, ZIP5 or ZnT1 in rats, but shows an inverse correlation with that of metallothioneins (MTs). This finding may be partly explained by the buffering role of metallothionein in intestinal absorption. The saturable transport of zinc is not simply determined only by the influx transporter, ZIP4, since three influx and efflux transporters are involved in the transport of zinc.

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“…Other transporters have been suggested to drive the distal reabsorption of heavy metals. Thus, Ducoudret et al [4] showed that Madin-Darby canine kidney (MDCK) cells, which share some properties of distal nephron cells, expressed a transporter, sensitive to pH, which transports Zn 2+ , Cd 2+ and Cu 2+ but not Fe 2+ , Mn 2+ or Co 2+ . Nagao et al [14] described in this cell line a metal transporter involved in the uptake of Co 2+ , Cu 2+ , Ni 2+ , Pb 2+ and Zn 2+ but not in the uptake of Fe 2+ or Mn 2+ .…”

Section: What Are the Chemical Forms Of Heavy Metal Transported In Thmentioning

confidence: 99%

Effect of Heavy Metals on, and Handling by, the Kidney

Barbier¹,

Jacquillet²,

Tauc³

et al. 2005

Nephron Physiol

Self Cite

375

183

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Heavy metals such as cadmium (Cd), mercury (Hg), lead (Pb), chromium (Cr) and platinum (Pt) are a major environmental and occupational hazard. Unfortunately, these non-essential elements are toxic at very low doses and non-biodegradable with a very long biological half-life. Thus, exposure to heavy metals is potentially harmful. Because of its ability to reabsorb and accumulate divalent metals, the kidney is the first target organ of heavy metal toxicity. The extent of renal damage by heavy metals depends on the nature, the dose, route and duration of exposure. Both acute and chronic intoxication have been demonstrated to cause nephropathies, with various levels of severity ranging from tubular dysfunctions like acquired Fanconi syndrome to severe renal failure leading occasionally to death. Very varied pathways are involved in uptake of heavy metals by the epithelium, depending on the form (free or bound) of the metal and the segment of the nephron where reabsorption occurs (proximal tubule, loop of Henle, distal tubule and terminal segments). In this review, we address the putative uptake pathways involved along the nephron, the mechanisms of intracellular sequestration and detoxification and the nephropathies caused by heavy metals. We also tackle the question of the possible therapeutic means of decreasing the toxic effect of heavy metals by increasing their urinary excretion without affecting the renal uptake of essential trace elements. We have chosen to focus mainly on Cd, Hg and Pb and on in vivo studies.

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Characterization of Zn2+ transport in Madin-Darby canine kidney cells

Cited by 8 publications

References 24 publications

The native TRPP2-dependent channel of murine renal primary cilia

The native TRPP2-dependent channel of murine renal primary cilia

<i>In Vitro</i> Study on the Transport of Zinc across Intestinal Epithelial Cells Using Caco-2 Monolayers and Isolated Rat Intestinal Membranes

Effect of Heavy Metals on, and Handling by, the Kidney

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