Parametric resonance and amplification of periodic disturbances in membranes containing ion channels with inactivation

Parametric resonance and amplification of periodic perturbations in the membrane transport of ions through channels with inactivation was studied in computational experiments. It has been shown that a periodic change in the membrane capacitance or in the applied electric current with a frequency approximately 2 omega 0 (omega 0--the own angular frequency of the membrane) may excite stable self-oscillations in the membrane with a frequency of approximately omega 0. For this to occur, the degree of the capacitance modulation m or the amplitude of the applied current i0 must exceed some critical values mcr and i0cr. Excitation of self-oscillations by alternating electric current of the frequency approximately 2 omega 0 has the characteristics of parametric resonance. This can be explained by the fact that the equivalent membrane inductance depends on ionic current and displays periodic changes with a frequency approximately 2 omega 0, as also does the current. Small-amplitude periodic changes in the capacitance (m less than mcr) with frequencies approximately 2 omega 0 may result in significant amplification of periodic perturbations with frequencies approximately omega 0.     

Power amplification in the mammalian cochlea

It was first suggested by Gold in 1948 [1] that the exquisite sensitivity and frequency selectivity of the mammalian cochlea is due to an active process referred to as the cochlear amplifier. It is thought that this process works by pumping energy to augment the otherwise damped sound-induced vibrations of the basilar membrane [2-4], a mechanism known as negative damping. The existence of the cochlear amplifier has been inferred from comparing responses of sensitive and compromised cochleae [5] and observations of acoustic emissions [6, 7] and through mathematical modeling [8, 9]. However, power amplification has yet to be demonstrated directly. Here, we prove that energy is indeed produced in the cochlea on a cycle-by-cycle basis. By using laser interferometry [10], we show that the nonlinear component of basilar-membrane responses to sound stimulation leads the forces acting on the membrane. This is possible only in active systems with negative damping [11]. Our finding provides the first direct evidence for power amplification in the mammalian cochlea. The finding also makes redundant current hypotheses of cochlear frequency sharpening and sensitization that are not based on negative damping.     

The role of electrostatic interactions in the membrane binding of melittin

The binding of melittin and the C-terminally truncated analogue of melittin (21Q) to a range of phospholipid bilayers was studied using surface plasmon resonance (SPR). The phospholipid model membranes included zwitterionic dimyristylphosphatidylcholine (DMPC) and dimyristylphosphatidylethanolamine (DMPE), together with mixtures DMPC/dimyristylphosphatidylglycerol (DMPG), DMPC/DMPG/cholesterol and DMPE/DMPG. Melittin bound rapidly to all membrane mixtures, whereas 21Q, which has a reduced charge, bound much more slowly on the DMPC and DMPC/DMPG mixtures reflecting the role of the initial electrostatic interaction. The loss of the cationic residues also significantly decreased the binding of 21Q with DMPC/DMPG/Cholesterol, DMPE and DMPE/DMPG. The role of electrostatics was also highlighted with NaCl in the buffer, which affected the way melittin bound to the different membranes, causing a more uniform, concentration dependant increase in response. The biosensor results were correlated with the conformation of the peptides determined by circular dichroism analysis, which indicated that high α-helicity was associated with high binding affinity. Overall, the results demonstrate that the positively charged residues at the C-terminus of melittin play an essential role in membrane binding, that modulation of peptide charge influences selectivity of binding to different phospholipids and that manipulation of the cationic regions of antimicrobial peptides can be used to modulate membrane selectivity.     

Organ temperature measurement in a microwave oven by resonance frequency shift

An experimental system has been developed that can indirectly measure temperature in a high-intensity microwave field over a broad range of conditions. A RF amplifier connected closed-loop around a high Q cavity oscillates at one of the natural modes of the oven. A bandpass filter selects the mode of interest. As the frozen sample is thawed, an increase in dielectric constant occurs, decreasing the resonance frequency of the cavity. Calibration of the system is performed by measuring the frequency shift for samples whose temperatures are known, Rotation of samples during thawing often causes oscillations of the resonance frequency. These oscillations are generated by asymmetric sample properties and geometry, and hot spots developed during the thaw. Development of a method that would predict hot spot location from these resonance frequency oscillations and permit modulation of the magnetron or sample rotation to minimize thermal runaway is suggested.     

Electromagnetically induced transparency in a magnetized plasma during oblique propagation of radiation

The parametric effect of electromagnetically induced transparency (EIT) is studied in the case of quasi-transverse propagation of an extraordinary wave in the vicinity of the upper hybrid resonance in a cold plasma. The question is investigated of whether the waves that propagate in a smoothly inhomogeneous medium (from the transparency region in the vicinity of the upper hybrid resonance into vacuum or in the opposite direction) can reach the EIT region. The features of the quasi-transverse propagation of an extraordinary wave at the electron cyclotron resonance frequency in the quasi-EIT regime are also considered. It is shown that, in this situation, the parametric effects modify the polarization of the wave, with the result that its absorption increases substantially (by one to two orders of magnitude).     

Nonlinear Right-Hand Polarized Wave in Plasma in the Electron Cyclotron Resonance Region

The propagation of a nonlinear right-hand polarized wave along an external magnetic field in subcritical plasma in the electron cyclotron resonance region is studied using numerical simulations. It is shown that a small-amplitude plasma wave excited in low-density plasma is unstable against modulation instability with a modulation period equal to the wavelength of the excited wave. The modulation amplitude in this case increases with decreasing detuning from the resonance frequency. The simulations have shown that, for large-amplitude waves of the laser frequency range propagating in plasma in a superstrong magnetic field, the maximum amplitude of the excited longitudinal electric field increases with the increasing external magnetic field and can reach 30% of the initial amplitude of the electric field in the laser wave. In this case, the energy of plasma electrons begins to substantially increase already at magnetic fields significantly lower than the resonance value. The laser energy transferred to plasma electrons in a strong external magnetic field is found to increase severalfold compared to that in isotropic plasma. It is shown that this mechanism of laser radiation absorption depends only slightly on the electron temperature.     

Effect of parametric resonance on the formation of waves with a broad multiharmonic spectrum during the development of two-stream instability

A cubically nonlinear multiharmonic theory of two-stream instability in a two-velocity relativistic electron beam is constructed with allowance for parametric resonance between harmonics of longitudinal waves of different types, as well as between wave harmonics of the same type. The effect of these two kinds of parametric resonance interaction on the development of two-stream instability is investigated. It is shown that parametric resonance between different types of longitudinal waves excited in a two-velocity beam can substantially affect the development of physical processes in the system under study. It is proposed to use parametric resonance between longitudinal waves of different types to form waves with a prescribed broad multiharmonic spectrum.     

Evidence from electron paramagnetic resonance for function-related conformation changes in the anion-transport protein of human erythrocytes

The erythrocyte membrane protein involved in anion transport (band 3) was isolated in its native lipid milieu in the form of leaky vesicles and then was spin-labelled with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)-meleimide (MalMe4PipO). The resulting electron paramagnetic resonance spectrum of band-3-bound MalMe4PipO was resolved into a rapid tumbling component and another, relatively immobile component. The percentage of the signal contributed by the mobile component (Q), was sensitive to various characteristic factors known to affect erythrocyte anion transport: Q was a hyperbolic function of chloride concentration displaying a half-saturation constant K1/2 similar to that of chloride transport. On the other hand Q showed a biphasic response to sulfate concentration, in line with the relatively high affinity of sulfate for the anion modifier site. Q was a saturable function of pH, either in presence of Cl- or SO4(-2), showing a pKa between pH 6.0 and 6.5, in analogy with the pH titration curve of Cl- and SO4(-2), transport. Spin-labelled vesicles treated with a covalent inhibitor of anion transport, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, were markedly less susceptible to changes in Cl- concentration. It is suggested that the electron paramagnetic resonance spectrum of MalMe4PipO covalently bound to the band-3 protein, reports conformational changes which are related to the anion-transport function of this protein.     

Stargazin interaction with alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors is critically dependent on the amino acid at the narrow constriction of the ion channel

The subunit GluR2 of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subfamily of ionotropic glutamate receptors (GluRs) features a single amino acid at the narrow constriction of the pore loop that is altered from glutamine to arginine by RNA editing. This so-called Q/R site has been shown to play an important role in the determination of the electrophysiological properties of AMPA receptor complexes as well as of trafficking to the plasma membrane. The protein stargazin has also been shown to modulate electrophysiological properties and trafficking to the plasma membrane of AMPA receptors. In this study we examined via a series of mutants of the Q/R site of the AMPA receptor GluR1 whether the amino acid at this position has any influence on the modulatory effects mediated by stargazin. To this end, we analyzed current responses of Q/R site mutants upon application of glutamate and kainate and determined the amount of mutant receptor protein in the plasma membrane in Xenopus oocytes. Desensitization kinetics of several mutants were analyzed in HEK293 cells. We found that the stargazin-mediated decrease in receptor desensitization, the slowing of desensitization kinetics, and the kainate efficacy were all dependent on the amino acid at the Q/R site, whereas the stargazin-mediated increase in trafficking toward the plasma membrane remained independent of this amino acid. We propose that the Q/R site modulates the interaction of stargazin with the transmembrane domains of AMPA receptors via an allosteric mechanism and that this modulation leads to the observed differences in the electrophysiological properties of the receptor.     

N-terminal-mediated homomultimerization of prestin, the outer hair cell motor protein

The outer hair cell lateral membrane motor, prestin, drives the cell's mechanical response that underpins mammalian cochlear amplification. Little is known about the protein's structure-function relations. Here we provide evidence that prestin is a 10-transmembrane domain protein whose membrane topology differs from that of previous models. We also present evidence that both intracellular termini of prestin are required for normal voltage sensing, with short truncations of either terminal resulting in absent or modified activity despite quantitative findings of normal membrane targeting. Finally, we show with fluorescence resonance energy transfer that prestin-prestin interactions are dependent on an intact N-terminus, suggesting that this terminus is important for homo-oligomerization of prestin. These domains, which we have perturbed, likely contribute to allosteric modulation of prestin via interactions among prestin molecules or possibly between prestin and other proteins, as well.     

Cytotoxic T lymphocytes from mice with soluble class I Q10 molecules in their serum are not tolerant to membrane-bound Q10

Q10 is a class I Qa-2 region-encoded molecule that is secreted by the liver and present in serum at high concentrations (about 10 to 60 micrograms/ml) in most strains of mice. The amino terminal portion of this molecule can also be expressed as an integral membrane protein by splicing the 5' end of the Q10 gene to the 3' end of H-2Ld and transfecting the hybrid gene into murine L cells. Because CTL primarily recognize polymorphic determinants controlled by the alpha 1 and alpha 2 domains of class I molecules and because the Q10d/Ld product expressed by transfected L cells includes the alpha 1 and alpha 2 domains of Q10d, we could address whether mice bearing serum Q10 were tolerant to this molecule at the CTL level. The results of these experiments demonstrate that Q10+ mice are able to generate H-2-unrestricted CTL activity against Q10d expressed on transfected L cells, and this response was not inhibitable by the addition of Q10-containing normal mouse serum. It is unlikely that this CTL activity is due to possible polymorphic differences in Q10 alleles, since semisyngeneic BALB/c (H-2d) mice, from which the Q10d hybrid gene construct was derived, are able to generate anti-Q10d effector cells. The Q10d molecule was shown to cross-react with H-2Ld, lending support to the concept that Qa genes can serve as donors for polymorphic sequences found in H-2K, -D, and -L. That mice can generate anti-Q10 CTL activity suggests that this soluble class I protein does not act as a toleragen for these cells. The implications of these findings for an understanding of self-tolerance are discussed.     

Evidence of a Hopf bifurcation in frog hair cells

The membrane potential of hair cells in the low-frequency hearing organ of the bullfrog, the amphibian papilla, sinusoidally oscillates at small amplitude in the absence of acoustical input. We stimulate the cell with a series of periodic currents close to this natural frequency and observe that its current-to-voltage transfer function is compressively nonlinear, having a large gain for small stimuli and a smaller gain for larger currents. Along with the spontaneous oscillation, this implies that the cell is poised close to a dynamical instability such as a Hopf bifurcation, because distant from the instability the transfer function becomes linear. The cell's frequency selectivity is enhanced for small stimuli. Simulations show that the cell's membrane capacitance is effectively reduced due to a current gain provided by this dynamical instability. We propose that the Hopf resonance is widely used by transducer cells on the sensory periphery to achieve small-signal amplification.     

Model analysis of nonlinear modification of neutrophil calcium homeostasis under the influence of modulated electromagnetic radiation of extremely high frequencies

The problem of resonance effects of electromagnetic radiation (EMR) on biological objects remained unsolved till now. Previously we demonstrated that low-intensity amplitude-modulated EMR of extremely high frequencies (EHF) modified the activity of mouse neutrophils in the synergistic reaction of calcium ionophore A23187 and phorbol ester PMA. The EHF EMR influence on the neutrophils was significant at the carrier frequencies of radiation within a narrow range of 41.8–42.05 GHz and at the modulation frequency of 1 Hz. The purpose of the work was the analysis of frequency-dependent modification of intracellular free calcium concentration ([Ca²⁺]_i) by modulated EHF EMR on the basis of a special model for [Ca²⁺]_i oscillations in the neutrophils. The calcium channels of plasma membrane were chosen as the action target of external modulation in the model. The computer simulation demonstrated the rise in [Ca²⁺]_i at the influence of the external field with a threshold dependence on the modulation amplitude. The effect depended heavily on a sequence of delivery of the chemical and electromagnetic stimuli. The narrow-band rise in [Ca²⁺]_i had a phase-frequency dependence. With the modulation amplitudes exceeding the threshold value, the rise in [Ca²⁺]_i of more than 50% of the initial level was observed at the frequency of about 1 Hz and in the phase range of 0.3–2.5 radians. The results of the model analysis are in good correspondence with the experimental data obtained before, namely, with the resonance modification of the neutrophil activity at the modulation frequency of 1 Hz and with the presence of the effect only at high concentrations of calcium ionophore.     

The Spatial Origins of Cochlear Amplification Assessed by Stimulus-Frequency Otoacoustic Emissions

Cochlear amplification of basilar membrane traveling waves is thought to occur between a tone’s characteristic frequency (CF) place and within one octave basal of the CF. Evidence for this view comes only from the cochlear base. Stimulus-frequency otoacoustic emissions (SFOAEs) provide a noninvasive alternative to direct measurements of cochlear motion that can be measured across a wide range of CF regions. Coherent reflection theory indicates that SFOAEs arise mostly from the peak region of the traveling wave, but several studies using far-basal suppressor tones claimed that SFOAE components originate many octaves basal of CF. We measured SFOAEs while perfusing guinea pig cochleas from apex to base with salicylate or KCl solutions that reduced outer-hair-cell function and SFOAE amplification. Solution effects on inner hair cells reduced auditory nerve compound action potentials (CAPs) and provided reference times for when solutions reached the SFOAE-frequency CF region. As solution flowed from apex to base, SFOAE reductions generally occurred later than CAP reductions and showed that the effects of cochlear amplification usually peaked ∼1/2 octave basal of the CF region. For tones ≥2 kHz, cochlear amplification typically extended ∼1.5 octaves basal of CF, and the data are consistent with coherent reflection theory. SFOAE amplification did not extend to the basal end of the cochlea, even though reticular lamina motion is amplified in this region, which indicates that reticular lamina motion is not directly coupled to basilar membrane traveling waves. Previous reports of SFOAE-frequency residuals produced by suppressor frequencies far above the SFOAE frequency are most likely due to additional sources created by the suppressor. For some tones <2 kHz, SFOAE amplification extended two octaves apical of CF, which highlights that different vibratory motions produce SFOAEs and CAPs, and that the amplification region depends on the cochlear mode of motion considered. The concept that there is a single “cochlear amplification region” needs to be revised.     

Sensitivity of ocellar interneurons of the honeybee to constant and temporally modulated light

Sinusoidally modulated and discrete light pulses, the parameters of which approximated natural light conditions, were used to determine the response characteristics of ocellar first-order interneurons of the worker honeybee (Apis mellifera carnica). Large ocellar interneurons which terminate within the brain (LB neurons) were recorded from intracellularly and were identified visually after dye injection. Absolute sensitivity of LB neurons to light flashes ranges from 4 X 10(9) quanta/cm2s (Q) for MOC1,7 neurons to 1 X 10(12) Q for MOC3,4. The slope of the response-intensity (R/I) functions, which were calculated for intensities between 2 X 10(9) and 4 X 10(13) Q, varies in different types of LB neurons. The strongest response is given by one group of median ocellar neurons. With constant light around 10(13) Q, most LB neurons exhibit oscillatory hyperpolarizations which, upon increasing the stimulus to even higher intensities (10(14)-10(15) Q), gradually evolve to a hyperpolarized plateau. The frequency of these oscillatory voltage fluctuations increases with the rate of modulation of the stimulating light and reaches maximum values at 5-15 Hz modulation frequency. Two groups of MOC neurons follow sinusoidally modulated light up to 32 +/- 8 Hz (n = 5) and 29 +/- 6 Hz (n = 3), respectively, whereas lateral ocellar neurons cut off at 17 +/- 5 Hz (n = 4). The possible role of LB neurons is discussed. They may be inactivated when the bee is flying in bright sunlight.     

Consequences of Location-Dependent Organ of Corti Micro-Mechanics

The cochlea performs frequency analysis and amplification of sounds. The graded stiffness of the basilar membrane along the cochlear length underlies the frequency-location relationship of the mammalian cochlea. The somatic motility of outer hair cell is central for cochlear amplification. Despite two to three orders of magnitude change in the basilar membrane stiffness, the force capacity of the outer hair cell’s somatic motility, is nearly invariant over the cochlear length. It is puzzling how actuators with a constant force capacity can operate under such a wide stiffness range. We hypothesize that the organ of Corti sets the mechanical conditions so that the outer hair cell’s somatic motility effectively interacts with the media of traveling waves—the basilar membrane and the tectorial membrane. To test this hypothesis, a computational model of the gerbil cochlea was developed that incorporates organ of Corti structural mechanics, cochlear fluid dynamics, and hair cell electro-physiology. The model simulations showed that the micro-mechanical responses of the organ of Corti are different along the cochlear length. For example, the top surface of the organ of Corti vibrated more than the bottom surface at the basal (high frequency) location, but the amplitude ratio was reversed at the apical (low frequency) location. Unlike the basilar membrane stiffness varying by a factor of 1700 along the cochlear length, the stiffness of the organ of Corti complex felt by the outer hair cell remained between 1.5 and 0.4 times the outer hair cell stiffness. The Y-shaped structure in the organ of Corti formed by outer hair cell, Deiters cell and its phalange was the primary determinant of the elastic reactance imposed on the outer hair cells. The stiffness and geometry of the Deiters cell and its phalange affected cochlear amplification differently depending on the location.     

Broad Tunable Nanoantenna Based on Graphene Log-Periodic Toothed Structure

A log-periodic toothed nanoantenna based on graphene is proposed, and its multi-resonance properties with respect to the variations of the chemical potential are investigated. The field enhancement and radar cross-section of the antenna for different chemical potentials are calculated, and the effect of the chemical potential on the resonance frequency is analyzed. In addition, the dependence of the resonance frequency on the substrate is also discussed. It is shown that large modulation of resonance intensity in log-periodic toothed nanoantenna can be achieved via turning the chemical potential of graphene. The tunability of the resonant frequencies of the antenna can be used to broad tuning of spectral features. The property of tunable multi-resonant field enhancement has great prospect in the field of graphene-based broadband nanoantenna, which can be applied in non-linear spectroscopy, optical sensor, and near-field optical microscopy.     

Differential effects of cholesterol on acyl chain order in erythrocyte membranes as a function of depth from the surface. An electron paramagnetic resonance (EPR) spin label study

The purpose of this work is to analyze the effects of cholesterol modulation on acyl chain ordering in the membrane of human erythrocytes as a function of depth from the surface. Partial cholesterol depletion was achieved by incubation of erythrocytes with liposomes containing saturated phospholipids, or with methyl-beta-cyclodextrin (MbetaCD). Cholesterol enrichment was achieved by incubation with liposomes formed by phospholipids/cholesterol, or with the complex MbetaCD/cholesterol. Acyl chain order was studied with electron paramagnetic resonance spectroscopy (EPR) using spin labels that sense the lipid bilayer at different depths. It is shown that the increase in cholesterol stiffens acyl chains but decreases the interaction among lipid headgroups, while cholesterol depletion causes the opposite behavior. It is likely that the observed cholesterol effects are related to those stabilizing the cholesterol-rich detergent-insoluble membrane domains (rafts), recently shown to exist in erythrocytes.     

Actively Tunable Fano Resonance Based on a T-Shaped Graphene Nanodimer

We present the strength modulation and frequency tuning of Fano resonance by employing a graphene nanodimer formed by two coplanar perpendicular nanostrips with different dimensions. The Fano resonance is induced by destructive interference between the bright dipole mode of a short nanostrip and the dark quadrupole mode of a long nanostrip. The strength, line width, and resonance frequency of the Fano resonance can be actively modulated by changing the spatial separation of those two graphene nanostrips and the Fermi energy of the graphene nanodimer, respectively, without re-fabricating the nanostructures. The tuning of the strength and resonance frequency can be attributed to the coupling strength and optical properties of graphene, respectively. Importantly, a figure of merit value as high as 39 is achieved in the proposed nanostructures. Our results may provide potential applications in optical switching and bio-chemical sensing.     

Two spatio-temporal filters in human vision

1. We have studied visual detection of a circular target moving across a spatially and/or temporally modulated background. Illumination, I _t , for threshold detection of the target has been measured as a function of background modulation frequency and changes in I _t associated with background modulation provide a means of determining the frequency response characteristics of visual channels. 2. Temporal frequency responses obtained with temporally modulated, spatially uniform backgrounds have pass-band characteristics and the temporal frequency for peak response increases with increase in mean background illumination. These temporal frequency responses resemble those of the de Lange (1954) filter, but the latter incorporates the incremental thresholds for steady backgrounds. 3. The amplitude of this temporal response saturates at low (40%) background modulation, decreases to zero as the target velocity falls to zero, and is maximum for a circular target of diameter 2°. 4. The spatial characteristics of this temporal filter were measured with a background field consisting of alternate steady and flickering bars. The resulting spatial frequency curve peaks at 1 cycle deg^-1 for all background illuminations and is independent of the background grating orientation. This spatial response differs significantly from the IMG spatial functions observed with a background grating (Barbur and Ruddock, 1980). 5. The spatial and temporal responses reviewed above exhibit similar parametric variations and we therefore associate them with a single spatiotemporal filter, ST2. 6. A second temporal response, with low-pass frequency characteristics, was observed with a background field consisting of two matched gratings, presented in spatial and temporal antiphase. This response has parametric properties similar to those of the IMG spatial response described previously by Barbur and Ruddock (1980), thus we associated the two sets of data with a single spatio-temporal filter, ST1. 7. We show that the ST2 responses can be obtained by combining ST1 responses, and we present a network incorporating the two filters. 8. We review other psychophysical studies which imply the activity of two spatio-temporal filters with properties of the kind revealed in our studies. We argue that filter ST1 has properties equivalent to those of X-type and filter ST2 has properties equivalent to those of Y-type electrophysiological mechanisms.