Biomedical subjects

A Laamarti

Publications and source records attributed to A Laamarti.

5 recordsLinked to original sources

PubMed1998

Ionic transport in macula densa cells.

Recent work has provided substantial insights into functional characteristics of macula densa (MD) cells. Microelectrode and patch-clamp experiments on the rabbit isolated thick ascending limb (TAL)/glomerulus preparation have shown that MD cells possess a furosemide-sensitive Na:K:2Cl cotransporter, an apical 41-pS K+ channel, and a dominant basolateral Cl- conductance. Increasing luminal fluid [NaCl] ([NaCl]L) results in furosemide-sensitive cell depolarization due to a rise in intracellular [Cl-] that stimulates basolateral electrogenic Cl- efflux. Intracellular pH (pHi) measurements show the presence of an apical Na:H exchanger that couples transepithelial Na+ transport to pHi. Experimental results and thermodynamic considerations allow estimation of intracellular [Na+] and [Cl-] ([Na+]i, [Cl-]i) under different conditions. When the Na:K:2Cl cotransporter is equilibrated (or in the presence of furosemide), [Na+]i and [Cl-]i are low (approximately 6 to 7 mM), whereas when the cotransporter is fully activated, [Na+]i and [Cl-]i increase substantially to approximately 70 and 20 mM, respectively. Finally, luminal addition of NH4+ produces cell acidification that depends on NH4+ apical transport rate through the Na:K:2Cl. Using a simple transport model for NH4+, the initial NH4+ influx rate in MD cells is comparable to the corresponding flux in TAL. This challenges the idea that MD cells have a low transport activity but supports our findings about large changes in intracellular concentrations as a function of [NaCl]L.

Animals↗

PubMed1998

[Colobomatous orbital cyst associated with microphthalmos. Apropos of a case].

Colobomatous orbital cyst with microphthalmos is a rare anomaly occurring during embryogenesis. The authors describe a case of colobomatous orbital cyst with microphthalmos in a three-month-old child underlying the difficulties of clinical diagnosis and emphasizing the role of radiologic investigations. It is only the histopathologic study which allows the final diagnosis. From the informations given by this observation, the authors discuss the pathogenic, diagnostic, histopathologic and therapeutic characteristics of this disease.

Coloboma↗

PubMed1995

Evidence for apical sodium proton exchange in macula densa cells.

These studies were performed to determine if changes in luminal sodium chloride concentration ([NaCl]) might alter macula densa intracellular pH. Isolated thick ascending limbs with attached glomeruli were bathed in a 150 mM NaCl Ringer's solution and perfused in vitro with a 25 mM NaCl solution; N-methyl-D-glucamine cyclamate was used to substitute for NaCl. Macula densa cells were loaded with BCECF and intracellular pH was monitored using a microscope based-dual excitation photometer system. Control intracellular pH for all experiments in which tubules were initially perfused with 25 mM NaCl averaged 7.22 +/- 0.06; N = 28. Increasing luminal [NaCl] from 25 to 150 mM elevated macula densa pH by 0.15 +/- 0.03 (N = 6; P < 0.05) while increasing just luminal [Na] from 25 to 150 mM alkalinized macula densa cells by 0.17 +/- 0.05 (N = 6; P < 0.05). In addition, there was a highly significant linear relationship between luminal [Na] and intracellular pH between 25 and 150 mM NaCl. Other studies were performed to assess the effects of amiloride, an inhibitor of Na:H exchange, on macula densa intracellular pH. Addition of amiloride, to the 25 mM NaCl perfusate acidified macula densa cells by 0.09 +/- 0.03 (N = 6; P < 0.001) and significantly attenuated the increase in pH obtained when luminal [NaCl] was raised from 25 to 150 mM. Other studies evaluated the effects of inhibition of Na:2Cl:K cotransport on macula densa pH.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

PubMed1995

Activation of Na:2Cl:K cotransport by luminal chloride in macula densa cells.

Changes in macula densa intracellular pH (pHi) were used to monitor the direction of flux mediated by the apical Na:2Cl:K cotransporter. At the macula densa, a decrease in luminal [Cl] ([Cl]1) from 60 to 1 mM produced cellular alkalinization secondary to a cascade of events involving a decrease in apical Na:2Cl:K cotransport, a fall in intracellular [Na] ([Na]i) and a stimulation of Na:H exchange. This is supported by the fact that 97% of the change in macula densa pHi with reduction in [Cl]1 was bumetanide-sensitive whereas 92% of this pH change was amiloride-sensitive. We found that, in the presence of 20 mM Na and 5 mM K, a [Cl]1 of 14.3 +/- 2.4 mM (N = 7) produced equilibrium of the apical cotransporter since the pHi obtained under this condition was identical to the pHi found after reducing the net ionic flux to zero with bumetanide. Using this value together with the expected stoichiometry for the bumetanide-sensitive cotransporter, it was estimated that the intracellular [Cl] ([Cl]i) at equilibrium (or in the presence of bumetanide) could be as low as 5 mM. Also, using a Hill number of 2 which is consistent with the present data, the affinity for [Cl]1 was found to be 32.5 mM. Under physiological luminal conditions prevailing at the end of the thick ascending limb (approximately 3.5 mM K, and approximately 25 to 30 mM NaCl), macula densa cells are probably operating close to equilibrium while maintaining a small net reabsorption of Na/K and Cl. Since macula densa cells appear capable of reducing [Cl]i to very low levels, a reabsorptive flux should continue to occur until [NaCl]1 is reduced to 18 mM.

Animals↗

PubMed1994

Basic properties and potential regulators of the apical K+ channel in macula densa cells.

These studies examine the properties of an apical potassium (K+) channel in macula densa cells, a specialized group of cells involved in tubuloglomerular feedback signal transmission. To this end, individual glomeruli with thick ascending limbs (TAL) and macula densa cells were dissected from rabbit kidney and the TAL covering macula densa cells was removed. Using patch clamp techniques, we found a high density (up to 54 channels per patch) of K+ channels in the apical membrane of macula densa cells. An inward conductance of 41.1 +/- 4.8 pS was obtained in cell-attached patches (patch pipette, 140 mM K+). In inside-out patches (patch pipette, 140 mM; bath, 5 mM K+), inward currents of 1.1 +/- 0.1 pA (n = 11) were observed at 0 mV and single channel current reversed at a pipette potential of -84 mV giving a permeability ratio (PK/PNa) of over 100. In cell-attached patches, mean channel open probability (N,Po, where N is number of channels in the patch and Po is single channel open probability) was unaffected by bumetanide, but was reduced from 11.3 +/- 2.7 to 1.6 +/- 1.3 (n = 5, p < 0.02) by removal of bath sodium (Na+). Simultaneous removal of bath Na+ and calcium (Ca2+) prevented the Na(+)-induced decrease in N.Po indicating that the effect of Na+ removal on N.Po was probably mediated by stimulation of Ca2+ entry. This interpretation was supported by studies where ionomycin, which directly increases intracellular Ca2+, produced a fall in N.Po from 17.8 +/- 4.0 to 5.9 +/- 4.1 (n = 7, p < 0.02). In inside-out patches, the apical K+ channel was not sensitive to ATP but was directly blocked by 2 mM Ca2+ and by lowering bath pH from 7.4 to 6.8. These studies constitute the first single channel observations on macula densa cells and establish some of the characteristics and regulators of this apical K+ channel. This channel is likely to be involved in macula densa transepithelial Cl- transport and perhaps in the tubuloglomerular feedback signaling process.

Animals↗