The Feasibility of Pharmacological Volume Control of Sickle Cells is Dependent on the Quantization of the Transport Pathways. A Model Study

✍ Scribed by Poul Bennekou

• Publisher: Elsevier Science
• Year: 1999
• Tongue: English
• Weight: 164 KB
• Volume: 196
• Category: Article
• ISSN: 0022-5193
• DOI: 10.1006/jtbi.1998.0819

✦ Synopsis

Normal erythrocytes are under physiological conditions characterized by low cation and high anion conductance. However, in the case of sickle cell anemia the erythrocytes contain a modified hemoglobin, HbS, which under low oxygen tension gives rise to sickling. This condition is preceded by an increase in cation conductance, especially due to the Ca 2+ -activated K + -channels, leading to net-efflux of KCl and thereby decreased cellular volume, which is part of the pathological condition.

A possible symptomatic treatment could be application of conductance blockers, targeting the Ca 2+ -activated K + -channel or the anion conductance, in order to minimize the passive transport of ions and solvent. It has been argued, that due to the high anion conductance, solute loss depended at moderately increased cation conductances on the cation only. Consequently the Ca 2+ -activated K + -conductance should be the target for attempts to modify solute loss.

It is shown that: knowledge of mean conductances (time averages) for pathways showing fluctuations are insufficient to predict the quantitative effect of conductance inhibitors, since inhibition is strongly dependent on the kinetics of the mechanisms mediating the translocation and a block of the high conductance anion pathway can be as effective as inhibition of the Ca 2+ -activated K + -conductance with regard to net salt loss.