Cell swelling stimulates the release of certain amino
Cell swelling stimulates the release of certain amino acids, in particular the non-protein amino methylphenidate hcl taurine, via a pathway which has the characteristics of a channel rather than a carrier , . Indeed, on the basis of pharmacological inhibition, it was suggested that volume-activated taurine release is via Cl− channels . In agreement with this suggestion, whole patch clamp studies have shown that volume-activated Cl− channels in C6 glioma, MDCK and IMCD cells are permeable to taurine, aspartate and glutamate , , . However, in some reports, two separate pathways were also proposed for taurine fluxes and chloride ions , , , .
In the human placenta, taurine is the most abundant amino acid and its concentration is 100- to 200-fold higher than the concentration in maternal blood .
Interestingly, several studies in fragments of villous tissue from human placenta, have shown volume-activated amino acid efflux via a pathway sensitive to classic inhibitors of anionic transporters (DIDS, NPPB and niflumic acid), consistent with the presence of volume-activated Cl− channels , . Some authors have proposed that volume-activated taurine efflux from placental tissue is mediated by a chloride channel , . In particular, the transport of taurine through the Maxi-chloride channel from placental tissue has been examined. Vallejos and Riquelme demonstrated that the permeabilities estimated from the shift in reversal potential of current–voltage curves after anion replacement, were as follows: chloride>taurine=glutamate=aspartate. In taurine symmetric conditions using equivalent Cl− concentrations, the slope conductance was around 62pS. The data showed that taurine and other amino acids diffuse through the Maxi-chloride channel, which could be of great importance as part of the mechanism involved in the volume regulation process in human placenta . As noted above, there is evidence that the Maxi-chloride channel is activated by cell swelling in neuroblastoma cells, rat cortical astrocytes and the renal cortical collecting duct cell line, among others , . Also, this channel may play a role in complex cellular regulation involving volume-dependent processes, such as those reported in C127i cells by Sabirov et al. who concluded that this channel serves as a pathway for swelling-induced ATP release . Thus, the apical Maxi-chloride channel from placenta is a possible candidate for Cl− and amino acid efflux in response to hyposmotic conditions including the taurine pathways (Fig. 3).
Placental chloride channels and pregnancy pathologies As previously mentioned, in the placenta, similar to other epithelia, chloride transport across placental membranes is crucial for various functions, thus direct or indirect alterations in Cl− channels could have a relationship with some diseases.
Summary Clearly, the interaction between solute transport and changes in electrical driving forces must be well understood in order to develop a model for the mechanism of materno-fetal chloride exchange. In particular, chloride channels allow only the passive materno-fetal chloride transport across the syncytiotrophoblast that is driven by the electrochemical gradient. Thus, the difference between the cytoplasmic and extracellular Cl− concentrations, together with the membrane voltage, determines whether the channel opening will lead to an influx or efflux of chloride ions. Substantial progress has been made in research on transport via chloride channels in the membranes of hSTB. Fig. 5 shows a summary diagram of the proposed chloride channels in the plasma membranes of hSTB and other mechanisms that involve chloride transport , . As was summarized in previous sections, only the Maxi-chloride channel has been extensively characterized with electrophysiological methods. The CFTR channel is not associated with a clear functional single-channel recording. Also, there is no single-channel candidate for apical DPC-sensitive chloride pathway and other such as Cl− channel calcium dependent. Additionally, chloride channels of the basal membranes are under current studies.