RED CELLS The effect of deoxygenation on whole-cell conductance of red blood cells from healthy individuals and patients with sickle cell disease
نویسندگان
چکیده
Red blood cells from patients with sickle cell disease (SCD) exhibit increased electrogenic cation permeability, particularly following deoxygenation and hemoglobin (Hb) polymerisation. This cation permeability, termed Psickle, contributes to cellular dehydration and sickling, and its inhibition remains a major goal for SCD treatment. Nevertheless, its characteristics remain poorly defined, its molecular identity is unknown, and effective inhibitors have not been established. Here, patch-clamp methodology was used to record whole-cell currents in single red blood cells from healthy individuals and patients with SCD. Oxygenated normal red blood cells had a low membrane conductance, unaffected by deoxygenation. Oxygenated HbS cells had significantly increased conductance and, on deoxygenation, showed a further rise in membrane conductance. The deoxygenation-induced pathway was variable in magnitude. It had equal permeability to Na and K , but was less permeable to NMDG and Cl . Conductance to Ca2 was also of a similar magnitude to that of monovalent cations. It was inhibited by DIDS (100 M), Zn2 (100 M), and by Gd3 (IC50 of approximately 2 M). It therefore shares some properties with Psickle. These findings represent the first electrical recordings of single HbS cells and will facilitate progress in understanding altered red blood cell cation transport characteristics of SCD. (Blood. 2007;109: 2622-2629)
منابع مشابه
The effect of deoxygenation on whole-cell conductance of red blood cells from healthy individuals and patients with sickle cell disease.
Red blood cells from patients with sickle cell disease (SCD) exhibit increased electrogenic cation permeability, particularly following deoxygenation and hemoglobin (Hb) polymerisation. This cation permeability, termed P(sickle), contributes to cellular dehydration and sickling, and its inhibition remains a major goal for SCD treatment. Nevertheless, its characteristics remain poorly defined, i...
متن کاملThe effect of deoxygenation on whole-cell conductance of red blood cells from normal individuals and sickle cell patients
متن کامل
Antioxidant Enzymes and Acute Phase Proteins Correlate with Marker of Lipid Peroxide in Adult Nigerian Sickle Cell Disease Patients
Objective(s) Sickle cell disease is a genetic disorder characterized by chronic haemolytic anaemia. Haemoglobin S containing red blood cells may be susceptible to oxidative stress due to imbalance between production of reactive oxygen species and the countering effect of the various antioxidants present in the body. Materials and Methods We evaluated some antioxidant enzymes which include gl...
متن کاملRed Blood Cell-Conditioned Media from Non-Alcoholic Fatty Liver Disease Patients Contain Increased MCP1 and Induce TNF-α Release
Background: Non-alcoholic fatty liver disease (NAFLD) constitutes a global pandemic. An intricate network among cytokines and lipids possesses a central role in NAFLD pathogenesis. Red blood cells comprise an important source of both cytokines and signaling lipids and have an important role in molecular crosstalk during immunometabolic deregulation. However, their role in NAFLD has not been tho...
متن کاملEffect of Thyroid Dysfunctions on Blood Cell Count and Red Blood Cell Indice
Abstract Background Thyroid hormones have a crucial role in metabolism and proliferation of blood cells. Thyroid dysfunction induces different effects on blood cells such as anemia, erythrocytosis leukopenia, thrombocytopenia, and in rare cases causes’ pancytopenia. It also alter RBC indices include MCV, MCH, MCHC and RDW. Thus this study attempted to evaluate effect of hypo & hyperthyroi...
متن کامل