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Effect of OPC-8490 on the membrane potentials and membrane currents of single guinea-pig myocytes.

The direct actions of OPC-8490 on mammalian myocardium were examined by determination of the drug's effects on the action potentials of isolated guinea-pig single ventricular cells and on the underlying ionic currents. OPC-8490 (10(-6) to 10(-4) M) did not alter the resting membrane potential, but rather produced a dose-dependent prolongation of the duration of the action potential. The amplitude of the action-potential plateau was also increased by OPC-8490. Whole-cell voltage clamp experiments revealed that OPC-8490 blocks myocardial delayed outward K+ current (IK), which regulates repolarization of the action potentials. However Ik1, which regulates the resting membrane potential, was not changed by OPC-8490. Ca current (ICa) was increased by OPC-8490 in a dose-dependent and reversible manner. These results suggest that OPC-8490 augments the plateau amplitude and increases the duration of the action potentials by not only increasing ICa, but also by decreasing delayed outward K+ currents. Moreover, OPC-8490 did not affect the intracellular concentration of cyclic AMP in single cells. The OPC-8490 increase in ICa was thus unlikely to be mediated by a process involving cyclic AMP.

Action Potentials↗

Effects of surface potential and membrane potential on the midpoint potential of cytochrome c-555 bound to the chromatophore membrane of Chromatium vinosum.

The values of midpoint potential (Em) of cytochrome c-555 bound to the chromatophore membranes of a photosynthetic bacterium Chromatium vinosum was determined under various pH and salt conditions. After a long incubation at high ionic concentrations in the presence of carbonylcyanide m-chlorophenylhydrazone, which was added to abolish electrical potential difference between the inner and outer bulk phases of chromatophore, the Em value was almost constant at pH values between 4.0 and 8.4. With the decrease of salt concentration, the pH dependence of the Em value became more marked. Under low ionic conditions, Em became more positive with the decrease of pH. Addition of salt made the value more positive or negative at pH values higher or lower than 4.5, respectively. Divalent cation salts were more effective than monovalent cation salts in producing the positive shift of Em at pH 7.8. The Em value became more positive when the electrical potential of the inner side of the chromatophore was made more positive by the diffusion potential induced by the K+ concentration gradient in the presence of valinomycin. These results were explained by a change of redox potential at the inner surface of the chromatophore membrane, at which the cytochrome is assumed to be situated, due to the electrical potential difference with respect to the outer solution induced by the surface potential or membrane potential change. The values for the surface potential and the net surface charge density of the inner surface of the chromatophore membrane were estimated using the Gouy-Chapman diffuse double layer theory.

Bacterial Chromatophores↗

Thermal membrane potential across charged membranes in 2-1 and 1-2 electrolyte solutions.

Measurements of thermal membrane potential across cation exchange membranes in MgCl2, CaCl2 and BaCl2 solutions and across anion exchange membranes in K2SO4, Na2SO4 and K2CO3 solutions were carried out. The magnitude of the thermal membrane potential for divalent counterions is lower than that for monovalent counterions. If the transport number of counterions in the membrane phase is unity, the slopes of the temperature coefficient of thermal membrane potential against logarithmic activities of counterion in the external solution are predicted to be--R/2F for 2-1 electrolytes with cation exchange membranes and R/2F for 1-2 electrolytes with anion exchange membranes, respectively.

Electrolytes↗

Thermal membrane potential across charged membranes in NaCl-NH4Cl and LiCl-NH4Cl solutions.

Measurements of the thermal membrane potential across cation exchange membranes were carried out by using aqueous solutions containing two 1-1 electrolytes, with an anion in common. The same solution was used on both sides of the membrane. In all cases a good linear relationship was observed between the thermal membrane potential delta psi and the temperature difference delta T (in the range delta T = +/- 10 degrees C). Assuming that the activity of one cation is equal to that of another cation in the solutions and the sum of transport numbers of cations is unity, the plot of delta psi/delta T vs logarithmic activity of one cation is linear with a slope of R/F. These experimental results are in agreement with a theory presented previously. From the analysis of thermal membrane potential in mixtures of electrolytes it is obtained that the cross coefficient of cation-cation interaction in membranes is negative and about 6 to 9% of the main coefficient.

Ammonium Chloride↗

Thermal membrane potential through charged membranes in electrolyte solutions.

Measurements of the thermal membrane potential across cation and anion exchange membranes were carried out by using the same solution of various 1-1 electrolytes on both sides of the membrane. In all cases a good linear relationship was observed between the thermal membrane potential increment psi and the temperature difference increment T. The slope of the linear plot varied with the concentration of the electrolyte. The value of increment psi/increment T versus logarithmic activity of the electrolyte plot was linear with a slope of +/- R/F if the transport number of counterion was unity. The magnitude of increment psi/increment T was independent of coion species but dependent on counterions. These experimental results are in agreement with a theory presented previously. The thermal membrane potential caused by the direct effect of temperature differences and that by the indirect effect arising from the changes in ionic and water chemical potentials due to the temperature difference are separately discussed.

Cations, Monovalent↗

Effects of quinine on membrane potential and membrane currents in identified neurons of Helix pomatia.

In the neurons B1, B2 and B3 of Helix pomatia, a systemic administration of quinine elicited: (1) a depolarization accompanied by an increase in membrane resistance (RM), sometimes preceded by a hyperpolarization associated with a decrease in RM; (2) a diminution in amplitude of action potentials and of afterhyperpolarization; (3) a reversible decrease of the amplitude of the inward current with a shift of the maximum amplitude and of the reversal to more negative potential values; (4) no change in the steady state inactivation curve of the inward current; and (5) a partly irreversible depression of the early outward current and of the late outward currents.

Animals↗

Comparative responses of human polymorphonuclear leukocytes obtained by counterflow centrifugal elutriation and Ficoll-Hypaque density centrifugation. II. Membrane potential changes, membrane receptor analysis, membrane fluidity, and analysis of the effects of the preparative techniques.

Standard preparative techniques for human polymorphonuclear leukocytes involves the sequential exposure of the PMN to dextran, Ficoll-Hypaque (FH) gradient centrifugation, and hypotonic stress. Counterflow centrifugal elutriation (CCE) allows isolation of PMN from whole blood without exposure to these potentially toxic substances. We have previously reported that PMN isolated by CCE release more superoxide on stimulation than do PMN isolated by standard techniques (FH PMN). In this report, we extend these observations and show that CCE and FH PMN have similar binding kinetics for the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and similar membrane fluidity. CCE PMN, however, were noted to have a more marked membrane depolarization on stimulation with FMLP than FH PMN. We show that exposure of purified CCE PMN to dextran increases their superoxide release on stimulation, as well as the available FMLP binding sites. Exposure of FH PMN to elutriation buffer increased their superoxide release on stimulation. It was also noted that both CCE and FH PMN re-exposed to FH increased available binding sites for FMLP. The possible reasons for these findings are discussed.

Adult↗

[Computer modeling the concentration characteristics of the membrane potential for polymeric membrane, separated non-homogeneous electrolyte solutions].

The influence of the concentration boundary layers on membrane potential (deltapsis) in a single-membrane system on basis of the Kedem-Katchalsky equations was described in cases of horizontally mounted neutral polymeric membrane separates non-homogeneous (mechanically unstirred) binary electrolytic solutions at different concentrations. Results of calculations of deltapsis as a function of ratio solution concentrations (Ch/Cl) at constant values of: concentration Rayleigh number (Rc), concentration polarization coefficient (zetas) and hydrostatic pressure (deltaP) were presented. Calculations were made for the case where on a one side of the membrane aqueous solution of NaCl at steady concentration 10(-3) mol x l(-1) (Cl) was placed and on the other aqueous solutions of NaCl at concentrations from 10(-3) mol x l(-1) to 2 x 10(-2) mol x l(-1) (Ch). Their densities were greater than NaCl solution's at 10(-3) mol x l(-1). It was shown that membrane potential depends on hydrodynamic state of a complex concentration boundary layer-membrane-concentration boundary layer, what is controlled by deltaP, Ch/Cl, Rc and zetas.

Biological Transport↗

[Computer modeling the hydrostatic pressure characteristics of the membrane potential for polymeric membrane, separated non-homogeneous electrolyte solutions].

On the basis of model equation depending the membrane potential deltapsis, on mechanical pressure difference (deltaP), concentration polarization coefficient (zetas), concentration Rayleigh number (RC) and ratio concentration of solutions separated by membrane (Ch/Cl), the characteristics deltapsis = f(deltaP)zetas,RC,Ch/Cl for steady values of zetas, RC and Ch/Cl in single-membrane system were calculated. In this system neutral and isotropic polymeric membrane oriented in horizontal plane, the non-homogeneous binary electrolytic solutions of various concentrations were separated. Nonhomogeneity of solutions is results from creations of the concentration boundary layers on both sides of the membrane. Calculations were made for the case where on a one side of the membrane aqueous solution of NaCl at steady concentration 10(-3) mol x l(-1) (Cl) was placed and on the other aqueous solutions of NaCl at concentrations from 10(-3) mol x l(-1) to 2 x 10(-2) mol x l(-1) (Ch). Their densities were greater than NaCl solution's at 10(-3) mol x l(-1). It was shown that membrane potential depends on hydrodynamic state of a complex concentration boundary layer-membrane-concentration boundary layer, what is controlled by deltaP, Ch/Cl, RC and zetas.

Biological Transport↗

A novel method for the determination of electrical potentials across cellular membranes. II. Membrane potentials of Acholeplasmas, Mycoplasmas, Streptococci and erythrocytes.

The membrane potentials of Acholeplasma laidlawii, Mycoplasma mycoides subsp. capri, Mycoplasma gallisepticum, Streptococcus faecalis and human erythrocytes have been determined by applying a novel technique. The membrane potentials were calculated simply from potassium concentrations determined by atomic absorption spectroscopy, and gravimetry. The versatility of the new technique is demonstrated by comparing our results with data obtained by different techniques.

Acholeplasma laidlawii↗

[Computer modeling the dependences of the membrane potential for polymeric membrane separated non-homogeneous electrolyte solutions on concentration Rayleigh number].

On the basis of model equation describing the membrane potential delta psi(s) on concentration Rayleigh number (R(C)), mechanical pressure difference (deltaP), concentration polarization coefficient (zeta s) and ratio concentration of solutions separated by membrane (Ch/Cl), the characteristics delta psi(s) = f(Rc)(delta P, zeta s, Ch/Cl) for steady values of zeta s, R(C) and Ch/Cl in single-membrane system were calculated. In this system neutral and isotropic polymeric membrane oriented in horizontal plane, the non-homogeneous binary electrolytic solutions of various concentrations were separated. Nonhomogeneity of solutions is results from creations of the concentration boundary layers on both sides of the membrane. Calculations were made for the case where on a one side of the membrane aqueous solution of NaCl at steady concentration 10(-3) mol x l(-1) (Cl) was placed and on the other aqueous solutions of NaCl at concentrations from 10(-3) mol x l(-1) to 2 x 10(-2) mol x l(-1) (Ch). Their densities were greater than NaCl solution's at 10(-3) mol x l(-1). It was shown that membrane potential depends on hydrodynamic state of a complex concentration boundary layer-membrane-concentration boundary layer, what is controlled by deltaP, Ch/Cl, Rc and Zeta(s).

Computer Simulation↗

Difluorophosphate as a 19F NMR probe of erythrocyte membrane potential.

Erythrocyte membrane potential can be estimated by measuring the transmembrane concentration (activity) distribution of a membrane-permeable ion. We present here the study of difluorophosphate (DFP) as a 19F NMR probe of membrane potential. This bicarbonate and phosphate analogue has a pKa of 3.7 +/- 0.2 (SD, n = 4) and therefore exists almost entirely as a monovalent anion at physiological pH. When it is incorporated into red cell suspensions, it gives two well resolved resonances that arise from the intra- and extracellular populations; the intracellular resonance is shifted approximately 130 Hz to higher frequency from that of the extracellular resonance. Hence the transmembrane distribution of DFP is readily assessed from a single 19F NMR spectrum and the membrane potential can be calculated using the Nernst equation. The membrane potential was independent of, DFP concentration in the range 4 to 59 mM, and haematocrit of the cell suspensions of 31.0 to 61.4%. The membrane potential determined by using DFP was 0.94 +/- 0.26 of that estimated from the transmembrane pH difference. The distribution ratios of intracellular/extracellular DFP were similar to those of the membrane potential probes, hypophosphite and trifluoroacetate. DFP was found to be transported across the membranes predominantly via the electrically-silent pathway mediated by capnophorin. Using magnetization transfer techniques, the membrane influx permeability-coefficient of cells suspended in physiological medium was determined to be 7.2 +/- 2.5 x 10(-6) cm s-1 (SD, n = 4).

Erythrocyte Membrane↗

Membrane potential of primitive red cells from chick embryo is a proton potential.

The membrane potential of primitive red cells from 4- and 6-day old chick embryos has been determined using the fluorescent dye Dis-C3-(5). At day 4 the membrane potential Em was -44 mV for pH 7.4 and 20 degrees C and -36 mV at day 6. Both values are far removed from the equilibrium potential for chloride, which is about -14 mV at day 6. Changes in the external potassium, sodium or chloride concentration were without effect on the membrane potential, except at very high potassium concentrations, where a small but significant depolarization was observed at day 6. The measurements gave the same results in the absence or presence of the anion exchange blocking agent DIDS. Three pieces of evidence indicate that the membrane potential of primitive red cells is primarily caused by an electrogenic H+ conductance: 1) The measured membrane potential of -36 mV at day 6 is close to the previously determined proton equilibrium potential (Baumann and Haller, 1983) EH + of -36 mV. 2) Addition of the electrosilent Cl-/OH- exchanger tributyltin causes a significant depolarization of about 20 mV at day 4 and about 14 mV at day 6. 3) Measurement of hydrogen ion fluxes demonstrate a potential dependent proton conductance, which increases with depolarization. These results indicate that large qualitative differences exist with regard to the mechanisms involved in the generation of membrane potential and hydrogen distribution between red cell and plasma of embryonic and adult chicken.

Animals↗