Calcium site specificity.
Early Ca2+-related tight junction events.


J Gen Physiol. 1997 Dec;110(6):727-40.

Lacaz-Vieira F.
Department of Physiology and Biophysics
Institute of Biomedical Sciences
University of Sao Paulo
Sao Paulo, Brazil
05508-900
lacaz@bmb.icbl.usp.br

The molecular mechanisms by which Ca2+ and metal ions interact with the binding sites that modulate the tight junctions (TJs) have not been fully described. Metal ions were used as probes of these sites in the frog urinary bladder. Basolateral Ca2+ withdrawal induces the opening of the TJs, a process that is abruptly terminated when Ca2+ is readmitted, and is followed by a complete recovery of the TJ seal. Mg2+ and Ba2+ were incapable of keeping the TJ sealed or of inducing TJ recovery. In addition, Mg2+ causes a reversible concentration-dependent inhibition of the Ca2+-induced TJ recovery. The effects of extracellular Ca2+ manipulation on the TJs apparently is not mediated by changes of cytosolic Ca2+ concentration. The transition elements, Mn2+ and Cd2+, act as Ca2+ agonists. In the absence of Ca2+, they prevent TJ opening and almost immediately halt the process of TJ opening caused by Ca2+ withdrawal. In addition, Mn2+ promotes an almost complete recovery of the TJ seal. Cd2+, in spite of stabilizing the TJs in the closed state and halting TJ opening, does not promote TJ recovery, an effect that apparently results on the TJs apparently is not mediated by changes of cytosolic Ca2+ concentration. The transition elements, Mn2+ and Cd2+, act as Ca2+ agonists. In the absence of Ca2+, they prevent TJ opening and almost immediately halt the process of TJ opening caused by Ca2+ withdrawal. In addition, Mn2+ promotes an almost complete recovery of the TJ seal. Cd2+, in spite of stabilizing the TJs in the closed state and halting TJ opening, does not promote TJ recovery, an effect that apparently results n the presence of Ca2+ (1 mM), indicates a high La3+ affinity for the Ca2+-binding sites. This ability of La3+ to open TJs in the presence of Ca2+ is a relevant aspect that must be considered when using La3+ in the evaluation of TJ permeability of epithelial and endothelial membranes, particularly when used during in vivo perfusion or in the absence of fixatives.

PMID: 9382899 [PubMed - indexed for MEDLINE]