Lamellar Porous Vermiculite Membranes for Boosting Nanofluidic Osmotic Energy Conversion

Lamellar membranes with two-dimensional nanofluidic channels hold great promise in harvesting osmotic energy from salinity gradients. However, the power density is often limited by the high transmembrane resistance primarily caused...

The ABCB1 3435C > T polymorphism influences docetaxel transportation in ovarian cancer

Objective To investigate the effect of the ATP-binding cassette transporter superfamily B member 1 gene ( ABCB1) 3435C > T single nucleotide polymorphism (SNP) on docetaxel transportation in ovarian cancer cells. Methods ES-2 and SKOV3 cells were transfected with an ABCB1 3435C > T recombinant plasmid, and mRNA expression was detected by real-time PCR. The MTT assay was used to detect the toxicity of docetaxel. High-performance liquid chromatography determined the drug concentration in different cell models to evaluate intracellular accumulation, and a transmembrane resistance experiment was used to assess permeability and evaluate the effect of P-gp activity on drug transportation. A tumor-bearing mouse model was established to evaluate the effect of ABCB1 3435C > T on docetaxel resistance. Results P-gp was overexpressed in cells transfected with the ABCB1 3435C > T plasmid, leading to a significant increase in drug resistance to docetaxel. ABCB1 3435C/wild-type transfection significantly promoted the transport of docetaxel mediated by P-gp compared with ABCB1 3435T/mutant transfection. Conclusion P-gp encoded by the ABCB1 variant allele appears to be more efficient at transporting docetaxel compared with the wild-type allele. The ABCB1 3435C > T SNP dramatically affected the efflux ability of P-gp against docetaxel, and may influence P-gp expression and activity.

DERIVING AN ELECTRIC CIRCUIT EQUIVALENT MODEL OF CELL MEMBRANE PORES IN ELECTROPORATION

Electroporation is the formation of reversible pores in cell membranes under a brief pulse of high electric field. Dynamics of pore formation during electroporation suggests that the transmembrane potential would settle approximately at the threshold transmembrane potential and the transmembrane resistance would decrease significantly from the state of relaxation. The current electric circuit equivalent models for electroporation containing time-invariant, static and passive components are unable to capture the pore dynamics. A biophysically-inspired electric circuit equivalent model containing dynamic components for membrane pores has been derived using biological parameters. The model contains a voltage-controlled resistor driven by a two-stage cascaded integrator that is activated through a voltage-gated switch. Simulation results with the derived model showed higher accuracy compared to a commonly used model, where the transmembrane resistance decreased million-fold at the onset of electroporation and the transmembrane potential settled at 99.5% of the critical transmembrane potential, thus enabling improved dynamic behavior modeling ability of the pores in electroporation. The derived model allows fast and reliable analysis of this biophysical phenomenon and potentially aids in optimization of various parameters involved in electroporation.

Electrical Feedback in the Cone Pedicle: A Computational Analysis

One of the fundamental principles of neuroscience is that direct electrical interactions between neurons are not possible without specialized electrical contacts, gap junctions, because the transmembrane resistance of neurons is typically much higher than the resistance of the adjacent extracellular space. However it has been proposed that in the retina direct electrical interactions between cones and second-order neurons occur due to the specific morphology of the cone synaptic terminal. This electrical mechanism could potentially explain the phenomenon of “negative feedback” from horizontal cells to cones and the recent finding that the tips of horizontal cell dendrites contain hemichannels has rekindled interest in the idea. We quantitatively evaluated the possibility that hemichannels and/or glutamate channels mediate electrical feedback from horizontal cells to cones. The calculations show that it is unlikely that an electrical mechanism plays a significant functional role because 1) the necessity of preserving adequate cone-to-horizontal-cell synaptic transmission limits the extracellular space resistance and the horizontal-cell dendritic transmembrane resistances to values at which the effectiveness of electrical feedback is very low and its electrical effect on the cone presynaptic membrane is negligible, 2) electrical feedback is most effective in the dark and weaker during light adaptation, which contradicts the experimental data, and 3) electrical negative feedback is associated with much stronger electrical positive feedback from horizontal cells to cones, a phenomenon that has never been reported. Therefore it is likely that negative feedback from horizontal cells to cones is chemical in nature.

POLYPYRROLE NANOWIRES GENERATION USING CHEMICAL SYNTHESIS THROUGH ION TRACK MEMBRANES

Polypyrrole nanocylinders were produced by non-galvanically (chemically) synthesizing polypyrrole within the pores of nanoporous polycarbonate ion track-etched membranes. The morphology of the nanowires was characterized by scanning electron microscopy. The electrical conductivity of the nanocylinders was calculated by leaving the nanocylinders fixed in the insulating template membrane and evaluating the transmembrane resistance.

The pH dependence of the contractile response of fatigued skeletal muscle

Following a period of intense repetitive stimulation (e.g., brief tetanic stimuli every second for 3 min), muscle isometric tension development is reduced by about 80%. This suppression is reversible at a high external pH (8.0) with a half time of 15–20 min, but if the external pH is low (6.4) or the buffer concentration is low, recovery is prevented. Inhibition of recovery is associated with a slowed rate of lactate loss, which may suggest that intracellular lactacidosis is the cause of the inhibition. Alternatively, a low external pH may affect recovery from fatigue quite independently of its effect on lactate efflux. The possibility that surface membrane properties are changed by fatigue in a pH-dependent fashion was examined by measuring the cable properties and action potentials of fatigued fibres at different external pH values. A low external pH during recovery from fatigue was shown to result in a prolonged membrane depolarization of 10–12 mV, an increased transmembrane resistance, and a prolonged action potential. At a high external pH transmembrane resistance is lowered by fatigue, the depolarization lasts only about 10–15 min, and there is a smaller effect on the action potential. While the fatigued fibre membrane does show a changed response that is dependent on external pH, it is not clear that this could be related to the suppression of contraction. Direct measurements of intracellular pH show a fall of about 0.4 to 0.5 pH units in the surface fibres following fatigue. This results from the lactic acid generated during activity. It is now clear that lactate crosses the membrane in association with protons and at least part of this flux is mediated by a specific carrier mechanism. Efflux is limited by the transmembrane pH gradient, which in turn depends on the extracellular buffer concentration in the diffusion limited space around the fibres. Intracellular lactacidosis in resting muscles can be generated by a reversal of the normal flux. Fibres can be loaded with lactate (L) by increasing the extracellular [H+][L−] product with a resultant fall in intracellular pH. Lactate loads similar to those seen in fatigued muscle simulate some but not all of the responses seen in the postfatigue state. The twitch is prolonged with a slow relaxation phase, an increased time to peak tension but with an increase in peak tension. The effects are reversible but usually result in a reduced contractile response following the washout. Tetanic tension is reduced, but the effect is small compared with that seen in fatigue. Relaxation from the tetanus is also slowed by the intracellular lactacidosis in a reversible fashion. It is concluded that intracellular lactacidosis is not the main cause of the suppressed tension found in the type of fatigue studied here but that the acidosis slows relaxation and may also prevent or slow some step in the transition from the fatigued to the normal state.

A kinetic model of membrane repair

Two microelectrodes are inserted into a Xenopus laevis egg. Rectangular current pulses are injected through one microelectrode and the voltage induced across the cell membrane is measured via the second electrode. The transmembrane resistance, as deduced from the injected current and the measured voltage, is taken as a measure of membrane integrity. The cell membrane is punctured with a glass fiber. The fall and subsequent recovery of transmembrane resistance are recorded. It is confirmed that cell membranes do exhibit repair and that repair is enhanced by the presence of calcium ion. A kinetic model of membrane repair is proposed.

The Effect of Calcium on the Desensitization of Membrane Receptors at the Neuromuscular Junction

Desensitization, as represented by the progressive decline in the electromotive effects of depolarizing agents at the neuromuscular junction, was studied by observing the time course of changes in effective transmembrane resistance during the prolonged application of 0.27 mM carbamylcholine to the postjunctional region of frog skeletal muscle fibers. The effective transmembrane resistance was measured by means of two intracellular microelectrodes implanted in the junctional region of single muscle fibers. When carbamylcholine was applied to the muscle there was an immediate decrease in the effective membrane resistance followed by a slower return toward control values which was identified as the phase of desensitization. When the calcium concentration was increased from 0 to 10 mM there was an approximately sevenfold increase in the rate of desensitization. On the other hand, an increase in the concentration of sodium from 28 to 120 mM caused a slowing of the rate of desensitization. Even in muscles depolarized by potassium sulfate, calcium increased the rate of desensitization while high concentrations of potassium tended to prolong the process. Some mechanisms by which calcium might exert these effects are discussed.