Daily functioning and symptom factors contributing to attitudes toward antipsychotic treatment and treatment adherence in outpatients with schizophrenia spectrum disorders.

BACKGROUND: Poor adherence and negative attitudes to treatment are common clinical problems when treating psychotic disorders. This study investigated how schizophrenia core symptoms and daily functioning affect treatment adherence and attitudes toward antipsychotic medication and to compare patients using clozapine or other antipsychotics. METHOD: A cross-sectional study with data from 275 patients diagnosed with schizophrenia spectrum disorder. Patients adherence, attitudes, insight and side-effects were evaluated using the Attitudes toward Neuroleptic Treatment scale. Overall symptomology was measured using the Brief Psychiatric Rating Scale (BPRS), the Health of the Nation Outcome Scale (HoNOS). The functioning was assessed using activities of daily living scale, instrumental activities of daily living scale and social functioning of daily living scale. RESULTS: Self-reported treatment adherence was high. Of the patients, 83% reported using at least 75% of the prescribed medication. Having more symptoms was related with more negative attitude towards treatment. There was a modest association with functioning and treatment adherence and attitude toward antipsychotic treatment. Attitudes affected on adherence in non-clozapine but not in clozapine groups. CONCLUSION: Early detection of non-adherence is difficult. Systematic evaluation of attitudes toward the treatment could be one way to assess this problem, along with optimized medication, prompt evaluation of side effects and flexible use of psychosocial treatments.

Association of somatic comorbidity and treatment adherence in patients with psychotic disorder.

BACKGROUND: Increased risk for somatic comorbidity in individuals with schizophrenia has been well established. In addition, psychiatric patients with somatic illnesses are more likely to have more psychiatric readmissions. Increased burden of treatment related to chronic somatic comorbidities may be associated with lower adherence to psychiatric medication. METHODS: Cross-sectional study of 275 patients with schizophrenia spectrum disorder. A general practitioner performed a complete physical health checkup for all participants, including a complete medical examination and laboratory tests. Patients' adherence, attitudes, insight, and side-effects were evaluated using the Attitudes toward Neuroleptic Treatment Scale. Overall symptomatology was measured using the Brief Psychiatric Rating Scale. Regression analysis was used to investigate interactions and associations among health beliefs, disease burden, and treatment adherence. Separate regression models were utilized to account for the complexity of health behavior and treatment adherence pathways. RESULTS: Patients' somatic comorbidity and health behavior were not associated with adherence or attitudes toward antipsychotic treatment. High dose of antipsychotics and obesity were related to the need for medical interventions, while a healthy diet reduced the risk. Higher BPRS score and older age were associated with having somatic symptoms. Somatic comorbidities had no negative effects on treatment adherence or attitudes. CONCLUSION: This study focuses on exploring possible associations between health beliefs and treatment adherence pathways in patients with psychotic disorders. Contrary to our hypotheses, we found no evidence to support our health belief and diseases burden models and their associations.

A neutralizing antibody against human DNA polymerase epsilon inhibits cellular but not SV40 DNA replication.

The contribution of human DNA polymerase epsilon to nuclear DNA replication was studied. Antibody K18 that specifically inhibits DNA polymerase activity of human DNA polymerase epsilon in vitro significantly inhibits DNA synthesis both when microinjected into nuclei of exponentially growing human fibroblasts and in isolated HeLa cell nuclei. The capability of this neutralizing antibody to inhibit DNA synthesis in cells is comparable to that of monoclonal antibody SJK-132-20 against DNA polymerase alpha. Contrary to the antibody against DNA polymerase alpha, antibody K18 against DNA polymerase epsilon did not inhibit SV40 DNA replication in vitro. These results indicate that DNA polymerase epsilon plays a role in replicative DNA synthesis in proliferating human cells like DNA polymerase alpha, and that this role for DNA polymerase epsilon cannot be modeled by SV40 DNA replication.

The effects of PMA and TFP and alterations in intracellular pH and calcium concentration on the membrane associations of phospholipid-binding proteins fodrin, protein kinase C and annexin II in cultured MDCK cells.

Annexin II, alpha-fodrin and protein kinase C (PKC) are associated with the cytoplasmic surface of the plasma membranes. When assayed with liposomes, they show affinity for acidic phospholipids and bind calcium ions. They also respond to or participate in cell signal transduction by altered membrane binding properties. In the present work we have studied the properties of these proteins in epithelial MDCK cells in response to elevated intracellular calcium ion concentration, lowered pH, treatment with tumor promoter phorbol myristoyl acetate (PMA) and calmodulin inhibitor trifluoperazine (TFP). In untreated polarized MDCK cells annexin II was seen both along the lateral walls and membranes of intracellular vesicles, fodrin was located along the lateral walls, whereas PKC was seen in the cytoplasm. There was no observable translocation of these proteins upon elevation of the intracellular calcium concentration using a calcium ionophore A23187. On the other hand, treatment with TFP led to a release of annexin II from the plasma membranes which was accompanied by a transient peak in the intracellular calcium. Treatment with PMA led to a loss of the cubic form of the cells, a slight elevation in the intracellular calcium concentration and a drop in the intracellular pH. Simultaneously fodrin was released from the lateral walls, but still remained insoluble in Triton X-100, PKC became associated with the intracellular membranes and fibers, whereas annexin II remained along the lateral walls. These changes could be prevented by clamping the intracellular pH neutral during PMA treatment. On the other hand, lowering of intracellular pH below 6.5 with the nigericin treatment led to a similar translocation of fodrin and PKC as PMA. This suggests that the protein redistribution is caused by cytoplasmic acidification and is due to an increased hydrophobicity and enhanced protonation of lipids and proteins. In contrast, no changes were seen in the annexin II distribution in response to altered pH. Hence, its release by TFP is presumably due to changes in the cationic properties of the inner phase of the plasma membrane. Thus, proteins which show similar binding properties with liposomes show different characteristics in their association with the intracellular membranes.

Role of vinculin in the maintenance of cell-cell contacts in kidney epithelial MDBK cells.

Microinjection of fluorophore-tagged cytoskeletal proteins has been a useful tool in studies of formation of focal adhesions (FA). We used this method to study the maintenance of adherens junctions (AJ) and tight junctions (TJ) of epithelial Madin-Darby bovine kidney cells. We chose alpha-actinin and vinculin as markers, because they are present both at adherens junctions and focal adhesions and their binding partners have been well characterized. Isolated FITC-labelled chicken alpha-actinin and vinculin were injected into confluent cells where they were rapidly incorporated both in FAs and AJs. The FAs remained unchanged, whereas cell-cell contacts began to fade within an hour after injection and the cells were joined to polykaryons having 5 to 13 nuclei. Short fragments of cell membranes containing injected proteins, actin, beta-catenin, cadherin, claudin, occludin and ZO-1 were visible inside the polykaryons indicating that both AJs and TJs were disintegrated as a single complex. Microinjected FITC-labelled vinculin head domain was also incorporated to both AJs and FAs, but instead of fusions it rapidly induced the detachment of the cells from the substratum probably due to high affinity of vinculin head to talin. Vinculin tail domain had no apparent effect on the cell morphology. Since small GTPases are involved in the building up of AJs, we injected active and inactive forms of cdc42 and rac proteins together with vinculin to see their effect. Active forms reduced the formation of polykaryons presumably by strengthening AJs, whereas inactive forms had no apparent effect. We suggest that excess alpha-actinin and vinculin uncouple the cell-cell adhesion junctions from the intracellular cytoskeleton which leads to fragmentation of junctional complexes and subsequent cell fusion. The results show that cell-cell adhesion sites are more dynamic and more sensitive than FAs to an imbalance in the amount of free alpha-actinin and intact vinculin.

Coated endosomal vesicles: sorting and recycling compartment for transferrin in BHK cells.

We have investigated receptor-mediated endocytosis of transferrin (Tf) in baby hamster kidney (BHK) cells, using fluorescence and electron microscopy, and by carrying out colocalization experiments with clathrin antibodies and a fluorescently tagged glycolipid. Early during internalization, Tf was found in small vesicles (100-150 nm in diameter) located at the cell periphery. The ligand remained associated with such vesicles when the latter concentrated towards the cell center, before ending up in the juxtanuclear area. Throughout this vesicular trafficking pathway, clathrin colocalized with Tf. We conclude that Tf is processed intracellularly via small coated endosomal vesicles (CEV) and is not delivered into large tubular endosomes (CURL; compartment for uncoupling receptors and ligands), typical for ligand trafficking to lysosomes. By determining the kinetics of Tf internalization and by comparing the flow of Tf to that of a fluorescent glycolipid, it can also be concluded that CEVs display sorting and recycling properties, implying that small vesicles can be shed from or fuse with CEVs. Acidic pH does not prevent the formation of CEVs, but their intracellular movement, towards the cell center, is impeded.

Effect of PMA on the integrity of the membrane skeleton and morphology of epithelial MDCK cells is dependent on the activity of amiloride-sensitive ion transporters and membrane potential.

The signaling pathways from an activation of protein kinase C (PKC) by phorbol myristate acetate (PMA) to the rearrangement of actin-based cytoskeleton and membrane skeleton of epithelial MDCK cells were studied by visualizing the cytoskeletal organization with immunofluorescence microscopy and by measuring intracellular pH, sodium ion concentration and membrane potential with the aid of fluorescent intracellular indicators. Upon PMA treatment the MDCK cells lost their cubic shape and acquired a spindle-like morphology. The stress fibers were depolymerized, and fodrin, the main component of the membrane skeleton, was released from the lateral walls to the cytosol. These changes were accompanied by depolarization of the cells, decrease in the intracellular pH and sodium ion concentration. In order to test the mutual correlation between the PMA-induced alterations we treated the cells with PMA in the presence of channel inhibitors or ionophores and in defined media. The effects of PMA on the membrane skeleton and morphology could be reversed in media lacking Na+ or K+ ions or by hyperpolarizing agents, dimethylamiloride and valinomycin, suggesting that the effects of PMA on the cytoskeleton were dependent on the ion gradients and membrane potential across the cell membrane. Moreover, the morphological changes and instabilization of the membrane skeleton of MDCK cells took place spontaneously without PMA in depolarizing conditions, in potassium gluconate buffer. We suggest that the membrane potential across the cell membrane of MDCK cells together with the activity of amiloride-sensitive cation transporters transmits signals in the protein kinase C (PKC) pathway leading from activation of PKC to fibroblast-like morphology and cytoplasmic localization of membrane skeleton components, features characteristic for cancer cells.

Intracellular sites involved in the biogenesis of bile canaliculi in hepatic cells.

Studies in hepatoma cells and hepatocytes have revealed that the biogenesis of bile canalicular membrane involves microvilli-lined vesicles (MLV), which are formed in well differentiated cells. The vesicles grow as a function of time and are presumably vectorially transported to cell surface contact sites of attached cells. We demonstrate that a fluorescent head group-labeled lipid analog, N-(lissamine rhodamine B sulfonyl)phosphatidylethanolamine (N-Rh-PE), after its exogenous insertion into the plasma membrane of HepG2 cells at 4 degrees C, accumulates in these microvilli-lined vesicles at 37 degrees C. This shows that the MLV are a target for plasma membrane-derived lipids. Furthermore, also the Golgi apparatus is involved in the formation of the vesicles. After initial accumulation of the fluorescent sphingolipid precursor, 6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]hexanoic acid (C6-NBD)-ceramide in the Golgi apparatus at 37 degrees C, prolonged incubation at 37 degrees C results in the appearance of NBD fluorescence in the microvilli-lined vesicles. The transport route for the Golgi-derived material to the developing bile canalicular vesicle is not an indirect pathway, i.e. involving transcytosis via the basolateral plasma membrane. This could be demonstrated by including bovine serum albumin (BSA) in the incubation media, a lipid scavenger that will remove any C6-NBD-lipids exposed at the basolateral membrane. At these conditions, lipid trafficking between the Golgi complex and MLV still occurred. We further demonstrate that the targeting from the Golgi apparatus to the bile canaliculus is also operational in isolated human hepatocytes. The latter results suggests that the Golgi complex is involved in both the formation of bile canaliculi and in bile secretion in fully differentiated cells.

Type XIII collagen: a novel cell adhesion component present in a range of cell-matrix adhesions and in the intercalated discs between cardiac muscle cells.

Recent analysis of type XIII collagen surprisingly showed that it is anchored to the plasma membranes of cultured cells via a transmembrane segment near its amino terminus. Here we demonstrate that type XIII collagen is concentrated in cultured skin fibroblasts and several other human mesenchymal cell lines in the focal adhesions at the ends of actin stress fibers, co-localizing with the known focal adhesion components talin and vinculin. This co-occurrence was also observed in rapidly forming adhesive structures of spreading and moving fibroblasts and in disrupting focal adhesions following microinjection of the Rho-inhibitor C3 transferase into the cells, suggesting that type XIII collagen is an integral focal adhesion component. Moreover, it appears to have an adhesion-related function since cell-surface expression of type XIII collagen in cells with weak basic adhesiveness resulted in improved cell adhesion on selected culture substrata. In tissues type XIII collagen was found in a range of integrin-mediated adherens junctions including the myotendinous junctions and costameres of skeletal muscle as well as many cell-basement membrane interfaces. Some cell-cell adhesions were found to contain type XIII collagen, most notably the intercalated discs in the heart. Taken together, the results strongly suggest that type XIII collagen has a cell adhesion-associated function in a wide array of cell-matrix junctions.

Induction of cell fusion in cultured fibroblasts and epithelial cells by microinjection of EGTA, GTP gamma S and antifodrin antibodies.

CaCl2, EGTA, GTP gamma S and anti-alpha-fodrin antibodies were injected into fibroblast-like IMR-33 cells and Madin-Darby bovine kidney (MDBK) epithelial cells cultured both in the presence and absence of cycloheximide and fetal calf serum. EGTA, GTP gamma S antifodrin antibody induced fusion of MDBK cells within one hour after injection. The cells formed polykaryons with up to 15 nuclei, reaching an average fusion index of 20%. IMR-33 cells fused at a slower kinetics and only upon injection of GTP gamma S or antifodrin antibodies. No fusions were seen in serum-deprived, quiescent cells. On the other hand, cycloheximide treatment did not prevent the fusions. The results show that cells can be induced to fuse by using agents that interfere with the regulation of the G-proteins, intracellular calcium level or membrane skeleton. We suggest that the putative fusogens are resident proteins of the plasma membrane which become exposed upon destabilization of the membrane skeleton.

Effects of adrenomedullin on hypertrophic responses induced by angiotensin II, endothelin-1 and phenylephrine.

We examined whether adrenomedullin (AM), a vasoactive peptide with significant expression and binding sites in the heart, modulates the hypertrophic response in cultured neonatal rat ventricular myocytes. Myocyte hypertrophy was induced by treating the cells with angiotensin II (Ang II), endothelin-1 (ET-1) or alpha-adrenergic agonist, L-phenylephrine (PHE). All treatments resulted in a hypertrophic response as reflected by increased protein synthesis and expression of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) genes. AM treatment resulted in a complete inhibition of the Ang II-induced increase in ANP and BNP gene expression and secretion. In contrast, no inhibitory effect was seen in either ET-1-induced natriuretic peptide gene expression or PHE-induced ANP and BNP gene expression and secretion. AM had only a modest effect on basal levels of natriuretic peptide secretion and gene expression. When AM mRNA levels in isolated neonatal rat myocytes treated for 48 h with Ang II, ET-1 or PHE were measured, only Ang II induced a consistent increase in AM gene expression. These results indicate that AM is not invariably associated with attenuation of the hypertrophic response but its effect is dependent on the stimulus activating myocyte hypertrophy. AM may form an important autocrine/paracrine growth-inhibitory loop in Ang II-induced myocyte hypertrophy.

Effect of lysophosphatidylcholine on salt permeability through the erythrocyte membrane under haemolytic conditions.

Human erythrocytes were incubated in haemolytic salt or sucrose media and the amount of potassium and haemoglobin released were monitored. In hypotonic NaCl and KCl solutions potassium release and haemolysis increased with time showing that the cell membrane had been injured and became permeable to intra- and extracellular cations which, due to intracellular haemoglobin, causes water influx and continuous haemolysis. Both potassium release and haemolysis remained, however, at their 2-minute level in the presence of LPC. Thus, LPC could reseal the membrane and prevent continuous salt fluxes. It protected erythrocytes from hypotonic haemolysis and the protection was more efficient in NaCl than in sucrose media. This suggests that the increase in the critical volume of erythrocytes caused by LPC occurs both in electrolyte and sucrose media, and the additional protection observed in electrolyte media is due to the resealing of the injured cell membrane by LPC. The repairing mechanism was mediated via the membrane lipids or integral proteins, since the time-course of haemolysis of erythrocytes swollen in NaCl media at the spectrin-denaturing temperature of 49.5 degrees C was similar to that at room temperature with and without LPC. LPC did not protect erythrocytes from colloid osmotic haemolysis caused by ammonia influx in an isotonic NH4Cl medium, but protected the cells from colloid osmotic haemolysis caused by sodium influx through nystatin-channels in NaCl media without any area or volume increase. Hence, LPC could not prevent ammonia influx through the lipid bilayer, but suppressed sodium influx through nystatin-channels presumably via LPC interference with cholesterol.

The hypotonic hemolysis and the protective action of lysophosphatidylcholine.

Lysophosphatidylcholine (LPC) protected against hypotonic hemolysis during rapid swelling of erythrocytes in spherocytic concentrations without any increase in the maximal cell volume. The total prelytic potassium release was increased, but the prelytic potassium release per cell was the same or decreased in the presence of LPC. The comparison of measured and calculated cell volume increase suggested that the prelytic potassium release must have been connected with a considerable sodium influx suggesting serious damage of the cell membrane already during swelling in the absence of LPC. Gradual swelling shifted hemolysis to more dilute solutions and LPC did not further increase the shift. We suggest that LPC protects the erythrocytes against hypotonic hemolysis during rapid swelling via a prevention of the initial membrane damage through altering the interaction between lipid bilayer and membrane cytoskeleton in the same way as occurs during incubation in a medium with low ionic strength.

Microscopic estimation of bacteria and cells in urine. II. A clinical study on the application of the theoretical considerations to clinical practice.

An improved technique for diagnosing acute urinary tract infections (UTI) by means of microscopic estimation of bacteria, leucocytes, erythrocytes and epithelial cells in urine was tested clinically in a total of 1,807 samples obtained from hospital departments. Marked bacteriuria (greater than or equal to 10(5) bacteria per ml of urine) was found microscopically in 13.1% of the urines. Of these 1.9% were falsely positive. Altogether 3.5% of the samples were falsely negative. When the sample collection was controlled carefully and detailed information on possible collection errors was given regularly, sensitivity and specificity indices of the microscopic technique were 85.3 and 98.1, respectively. Microscopic finding of cocci, e.g. Enterococci and Str. agalactiae, was more difficult than that of rods. Alongside bacteriuria, finding of leucocytes (greater than 5 leucocytes per microscopic field) was of great importance for UTI diagnostics, and it strengthened further the microscopic diagnosis, while erythrocytes and epithelial cells were of very poor significance for UTI diagnosis. The results show that the microscopic technique described here is a reliable and suitable method for UTI diagnostics in routine clinical laboratories which examine daily large numbers of samples, most of them negative.

The effect of cell swelling rate on the permeability and mechanical properties of the erythrocyte membrane.

A theoretical C-state model based on a thermodynamic equilibrium between water and chloride ions was used to calculate the cell volume of erythrocytes in hypotonic NaCl or sucrose media from information on the intracellular concentrations of cytoplasmic compounds and the area and volume distributions of erythrocytes in an isotonic reference state. Using various assumptions regarding prelytic potassium release and the corresponding sodium influx into cells swollen to a spherical mode, theoretical curves for the total amount of potassium released and cells haemolyzed as a function of the ambient osmotic pressure were generated and compared with the experimental results. The mechanical properties of the cell membrane in NaCl media during rapid water influx do not allow the cells to reach a spherical shape without membrane damage, which makes the membrane permeable to cations and also to haemoglobin. Reduction of the swelling rate diminishes the membrane injury and increases the protective role of potassium efflux in preventing haemolysis, but the cell membrane still is injured during sphering.

The kinetics of drug-membrane interactions in human erythrocytes.

The time course of the shape transformations and vesicle release in human erythrocytes caused by lysophosphatidylcholine and chlorpromazine was monitored using a light microscope-video recording technique. The time required for the erythrocytes to reach a stage I echinocytic shape decreased from 4.0 to 2.0 s, when the concentration of the lysophosphatidylcholine solution injected was increased from 1 to 25 microM. The time required to reach stage II decreased from 8.3 to 3.5 s and that required for vesicle release and the formation of stage IV spherocytes decreased from 78.0 to 11.6 s. Correspondingly, the time needed for the formation of stage I stomatocytes decreased from 2.3 to 1.0 s and that for stage II stomatocytes from 3.1 to 2.0 s, when the ambient chlorpromazine concentration was increased from 50 to 200 microM. The kinetics of the shape transformations of the erythrocytes were dependent on the ambient drug concentration. The rate of shape transformations could be predicted from a formula derived for the kinetics of the incorporation of the detergent into the cell membrane, providing that the affinity coefficient and mass transfer coefficient for drugs changed as a function of the free drug concentration. The results give a time scale for the drug-membrane interactions, i.e., the formation of stages I and II for drug-lipid bilayer interactions and the release of vesicles for drug-cytoskeleton interactions.

The kinetics of drug-membrane interactions in human erythrocytes from neonates.

The kinetics of drug-membrane interactions of erythrocytes from neonates were compared with those from adults by monitoring the time course of the shape transformations and vesicle release caused by drugs, using a light microscope--video recording technique. Both crenation caused by lysophosphatidylcholine (LPC) and cupping caused by chlorpromazine (CPZ) took place more slowly in the neonatal cells than in the cells from adults. The equilibrium concentrations of LPC and CPZ in erythrocytes did not differ significantly between the neonates and adults, however. The slower responses of the neonatal erythrocytes can be explained by the presence of negatively charged phosphatidylethanolamine and phosphatidylserine in the outer layer of the erythrocyte membrane, which may reduce the rate of incorporation of amphipathic LPC and attract cationic CPZ to remain in the outer membrane layer, lowering the rate of inward bending of the membrane normally caused by CPZ.

Effects of glutaraldehyde and critical point drying on the shape and size of erythrocytes in isotonic and hypotonic media.

Scanning electron microscopy (SEM) was applied to studies on osmotically swollen erythrocytes fixed by a method using increasing concentrations of glutaraldehyde (GA), OsO4 as a post fixative, and critical point drying (CPD). This fixation method prevented the osmotic effect of GA itself and preserved the cellular equilibrium shape intact in various media, i.e. discocytes in an isotonic medium and ellipsoids or spheres and ghosts in a hypotonic medium. The discocytes were reduced less in diameter and area than the ellipsoids and spheres during CPD, but the degree of volume shrinkage was of the same magnitude (approx. 73%) regardless of the cell shape. The shrinkage of the discocytes was advanced until the dry volume (approx. 29 microm3) was reached, while the shrinkage of the osmotically swollen cells ceased earlier. A miniaturization process coupled with solvent evaporation is suggested as an explanation for this. The osmotic swelling of erythrocytes was studied quantitatively with the aid of SEM micrographs. The increase in volume was about 60%, which is in agreement with the values obtained by light microscopy for unfixed and GA-fixed cells in the present work and with those reported in the literature.

Location and identification of colloidal gold particles on the cell surface with a scanning electron microscope and energy dispersive analyzer.

The use of colloidal gold particles for locating cell surface components by scanning electron microscopy (SEM) has been restricted due to difficulties in the identification of these gold particles under SEM. It is shown here how the gold particles bound to cell surfaces can be located and identified under SEM using the secondary electron imaging (SEI) mode with an energy dispersive X-ray microanalyzer (EDS). This enables reliable identification of gold particles and good quality micrographs of the cells to be achieved at the same time. The distribution of receptors for two lectins, concanavalin A (ConA) and wheat germ agglutinin (WGA), on the surface of cultured Raji cells and human erythrocytes is presented as an example. Raji cells and erythrocytes were fixed with glutaraldehyde, post-fixed with a glutaraldehyde-tannic acid mixture and then incubated with ConA- or WGA-coated gold particles. After dehydration and critical point drying, the specimen filters were mounted on copper stubs and coated with carbon. The cells were examined on a JEOL TEMSCAN 100CX II electron microscope. The gold particles could be identified with the EDS analyzer, which was able to detect the Au spectrum when the electron beam was focused on single gold particles using a magnification of 100,000 or more. High-resolution photographs of the same cells were obtained up to the same magnification of 100,000.

The effect of an osmotic pressure gradient and lysophosphatidylcholine on the transient and constant potassium permeability properties of the erythrocyte membrane.

The rate constant of 86Rb efflux and total potassium release from erythrocytes under the influence of lysophosphatidylcholine (LPC) and osmotic pressure gradients were compared. Both osmotic pressure gradients and LPC caused a transient increase in the potassium permeability of the erythrocyte membrane. In hypotonic media without or in the presence of LPC this sudden increase is completely reversible, since the rate constant of rubidium efflux from unhaemolyzed cells, which is an indicator for the continuous potassium release, remained the same as measured in an isotonic NaCl medium without detergents. The potassium release was more pronounced in the presence of LPC and may have a protective effect against haemolysis. In an isotonic NaCl or sucrose medium, LPC caused a transient potassium release probably due to incorporation of LPC into the membrane and vesicle release, but also an increase in the rate constant of rubidium efflux due to change in the membrane structure connected with vesicle release.