Intrinsic Rectification Research Articles

A Dramatic Odd–Even Oscillating Behavior for the Current Rectification and Negative Differential Resistance in Carbon‐Chain‐Modified Donor–Acceptor Molecular Devices

AbstractThe donor–acceptor molecule is the only molecule that features a real intrinsic rectification. However, all investigations in the last decades showed that rectification behaviors of such molecules are not promising since their rectification ratio is only on the order of 10. Use of carbon chains Cn to serve as spacers is reported, along with attempts to modulate electrical behavior of the donor–acceptor molecule. Calculations using the first‐principles method show that electrical behavior is indeed altered substantively, and a particular regularity can be clearly observed, i.e., a dramatic odd–even oscillation for electronic behavior with increasing carbon‐chain length n. For models with even‐n carbon chains, the rectification ratio is small (30), and no negative differential resistance (NDR) behavior is detected, but the rectifying performance of models with odd‐n carbon chains is tremendously improved and rectification ratios on the order of 50 to 400 can be achieved, alongside a large NDR. This study thus suggests that using a suitable spacer might be an effective way to significantly boost electrical characteristics, including rectifying performance, of the donor–acceptor molecule.

Bipolar spin diode based on a bent graphene nanoribbon

Using the nonequilibrium Green's function method, we investigate the bias-driven spin transport through a graphene nanoribbon device, which consists of a central bent junction coupled to a zigzag-edge source and an armchair-edge drain. Due to the zigzag-armchair structural transformation and the possible symmetry-matching between the bands of the source and drain, remarkable intrinsic spin rectification effects are observed, and the rectification coefficient depends strongly on the width of the drain. When the two electrodes with quite similar width are both transversely symmetrical and the drain is a semiconductor, the rectification coefficient could be up to 104%. Our results provide an efficient possibility for designing nanoscale spin rectifier, especially for bipolar spin diode.

Channel-forming activities in the glycosomal fraction from the bloodstream form of Trypanosoma brucei.

BackgroundGlycosomes are a specialized form of peroxisomes (microbodies) present in unicellular eukaryotes that belong to the Kinetoplastea order, such as Trypanosoma and Leishmania species, parasitic protists causing severe diseases of livestock and humans in subtropical and tropical countries. The organelles harbour most enzymes of the glycolytic pathway that is responsible for substrate-level ATP production in the cell. Glycolysis is essential for bloodstream-form Trypanosoma brucei and enzymes comprising this pathway have been validated as drug targets. Glycosomes are surrounded by a single membrane. How glycolytic metabolites are transported across the glycosomal membrane is unclear.Methods/Principal FindingsWe hypothesized that glycosomal membrane, similarly to membranes of yeast and mammalian peroxisomes, contains channel-forming proteins involved in the selective transfer of metabolites. To verify this prediction, we isolated a glycosomal fraction from bloodstream-form T.brucei and reconstituted solubilized membrane proteins into planar lipid bilayers. The electrophysiological characteristics of the channels were studied using multiple channel recording and single channel analysis. Three main channel-forming activities were detected with current amplitudes 70–80 pA, 20–25 pA, and 8–11 pA, respectively (holding potential +10 mV and 3.0 M KCl as an electrolyte). All channels were in fully open state in a range of voltages ±150 mV and showed no sub-conductance transitions. The channel with current amplitude 20–25 pA is anion-selective (P K+/P Cl−∼0.31), while the other two types of channels are slightly selective for cations (P K+/P Cl− ratios ∼1.15 and ∼1.27 for the high- and low-conductance channels, respectively). The anion-selective channel showed an intrinsic current rectification that may suggest a functional asymmetry of the channel's pore.Conclusions/SignificanceThese results indicate that the membrane of glycosomes apparently contains several types of pore-forming channels connecting the glycosomal lumen and the cytosol.

Electronic transport through zigzag/armchair graphene nanoribbon heterojunctions

The electronic transport properties of a graphene nanoribbon (GNR) are known to be sensitive to its width, edges and defects. We investigate the electronic transport properties of a graphene nanoribbon heterojunction constructed by fusing a zigzag and an armchair graphene nanoribbon (zGNR/aGNR) side by side. First principles results reveal that the heterojunction can be either metallic or semiconducting, depending on the width of the nanoribbons. Intrinsic rectification behaviors have been observed, which are largely sensitive to the connection length between the zGNR and aGNR. The microscopic origins of the rectification behavior have been revealed. We find that the carrier type can alter from electrons to holes with the bias voltage changing from negative to positive; the asymmetrical transmission spectra of electrons and holes induced by the interface defects directly results in the rectification behavior. The results suggest that any methods which can enhance the asymmetry of the transmission spectra between holes and electrons could be used to improve the rectification behavior in the zGNR/aGNR heterojunction. Our findings could be useful for designing graphene based electronic devices.

Rectification in three-terminal graphene junctions

Nonlinear electrical properties of graphene-based three-terminal nanojunctions are presented. Intrinsic rectification of voltage is observed up to room temperature. The sign and the efficiency of the rectification can be tuned by a gate. Changing the charge carrier type from holes to electrons results in a change in the rectification sign. At a bias <20 mV and at a temperature below 4.2 K the sign and the efficiency of the rectification are governed by universal conductance fluctuations.

KirBac1.1: It's An Inward Rectifying Potassium Channel

The structures of KirBac1.1 and KirBac3.1 have been used extensively to generate in silico homology models of eukaryotic Kir channels and to explore ion permeation, gating and drug-channel interactions by computational approaches. Functional studies of KirBac1.1 have been limited to 86Rb+ flux assays, but we have now succeeded in measuring voltage-clamp currents of KirBac1.1 reconstituted in giant liposomes. Using the patch-clamp technique, we recapitulate the results of 86Rb+ flux experiments, showing that KirBac1.1 currents are potassium-selective, blocked by barium, and inhibited by PIP2. These findings suggest that KirBac1.1 channels are functionally similar to eukaryotic Kir channels. Like the weak inward rectifiers Kir1.1 and Kir6.2, introduction of a negative charge at the “rectification controller” residue in the inner cavity of KirBac1.1 (I138D) confers strong inward rectification (i.e. steep voltage-dependent block by spermine). Steady state single channel currents of KirBac1.1 show multiple subconductance levels and gating modes in 150 mM symmetrical K+. However, similar to eukaryotic Kir channels, single channel amplitudes exhibit mild intrinsic inward rectification, with a maximum conductance at ∼56 pS (-100 mV), and open probability is higher at positive potentials. Multiple conductance states are still present in single channel currents of other permeant ions such as Rb+ and Tl+. However, similar to many K+ channels, including KcsA, Rb+ and Tl+ single channel currents show increased mean open time and decreased conductance. We find that KirBac1.1(T142C), equivalent to the Kir6.2 high P(o) mutant L164C, also has a high open probability and is effectively blocked by Cd+. These electrophysiological results confirm that KirBac1.1 is a bona fide inward rectifying K+ channel and a tractable model for study of the molecular basis of inward rectification, permeation and gating in eukaryotic Kir channels.

The two-pore channel TPK1 gene encodes the vacuolar K + conductance and plays a role in K + homeostasis

The Arabidopsis thaliana genome contains five genes that encode two pore K+ (TPK) channels. The most abundantly expressed isoform of this family, TPK1, is expressed at the tonoplast where it mediates K+ -selective currents between cytoplasmic and vacuolar compartments. TPK1 open probability depends on both cytoplasmic Ca2+ and cytoplasmic pH but not on the tonoplast membrane voltage. The channel shows intrinsic rectification and can be blocked by Ba2+, tetraethylammonium, and quinine. TPK1 current was found in all shoot cell types and shows all of the hallmarks of the previously described vacuolar K (VK) tonoplast channel characterized in guard cells. Characterization of TPK1 loss-of-function mutants and TPK1-overexpressing plants shows that TPK1 has a role in intracellular K+ homeostasis affecting seedling growth at high and low ambient K+ levels. In stomata, TPK1 function is consistent with vacuolar K+ release, and removal of this channel leads to slower stomatal closure kinetics. During germination, TPK1 contributes to the radicle development through vacuolar K+ deposition to provide expansion growth or in the redistribution of essential minerals.

Charges in the Cytoplasmic Pore Control Intrinsic Inward Rectification and Single-Channel Properties in Kir1.1 and Kir2.1 Channels

An E224G mutation of the Kir2.1 channel generates intrinsic inward rectification and single-channel fluctuations in the absence of intracellular blockers. In this study, we showed that positively charged residues H226, R228 and R260, near site 224, regulated the intrinsic inward rectification and single-channel properties of the E224G mutant. By carrying out systematic mutations, we found that the charge effect on the intrinsic inward rectification and single-channel conductance is consistent with a long-range electrostatic mechanism. A Kir1.1 channel where the site equivalent to E224 in the Kir2.1 channel is a glycine residue does not show inward rectification or single-channel fluctuations. The G223K and N259R mutations of the Kir1.1 channel induced intrinsic inward rectification and reduced the single-channel conductance but did not generate large open-channel fluctuations. Substituting the cytoplasmic pore of the E224G mutant into the Kir1.1 channel induced open-channel fluctuations and intrinsic inward rectification. The single-channel conductance of the E224G mutant showed inward rectification. Also, a voltage-dependent gating mechanism decreased open probability during depolarization and contributed to the intrinsic inward rectification in the E224G mutant. In addition to an electrostatic effect, a close interaction of K(+) with channel pore may be required for generating open-channel fluctuations in the E224G mutant.

Functional Roles of Charged Amino Acid Residues on the Wall of the Cytoplasmic Pore of Kir2.1

It is known that rectification of currents through the inward rectifier K+ channel (Kir) is mainly due to blockade of the outward current by cytoplasmic Mg2+ and polyamines. Analyses of the crystal structure of the cytoplasmic region of Kir2.1 have revealed the presence of both negatively (E224, D255, D259, and E299) and positively (R228 and R260) charged residues on the wall of the cytoplasmic pore of Kir2.1, but the detail is not known about the contribution of these charged residues, the positive charges in particular, to the inward rectification. We therefore analyzed the functional significance of these charged amino acids using single/double point mutants in order to better understand the structure-based mechanism underlying inward rectification of Kir2.1 currents. As a first step, we used two-electrode voltage clamp to examine inward rectification in systematically prepared mutants in which one or two negatively or positively charged amino acids were neutralized by substitution. We found that the intensity of the inward rectification tended to be determined by the net negative charge within the cytoplasmic pore. We then used inside-out excised patch clamp recording to analyze the effect of the mutations on blockade by intracellular blockers and on K+ permeation. We observed that a decrease in the net negative charge within the cytoplasmic pore reduced both the susceptibility of the channel to blockade by Mg2+ or spermine and the voltage dependence of the blockade. It also reduced K+ permeation; i.e., it decreased single channel conductance, increased open-channel noise, and strengthened the intrinsic inward rectification in the total absence of cytoplasmic blockers. Taken together, these data suggest that the negatively charged cytoplasmic pore of Kir electrostatically gathers cations such as Mg2+, spermine, and K+ so that the transmembrane pore is sufficiently filled with K+ ions, which enables strong voltage-dependent blockade with adequate outward K+ conductance.

Ion Channels of Alamethicin Dimer N-Terminally Linked by Disulfide Bond

A covalent dimer of alamethicin Rf30 was synthesized by linking the N-termini by a disulfide bond. When the dimer peptides were added to the cis-side of a diphytanoyl PC membrane, macroscopic channel current was induced only at cis positive voltages. The single-channel recordings showed several conductance levels that were alternately stabilized. These results indicate that the dimer peptides form stable channels by N-terminal insertion like alamethicin and that most of the pores are assembled from even numbers of helices. Taking advantages of the long open duration of the dimer peptide channels, the current-voltage ( I- V) relations of the single-channels were obtained by applying fast voltage ramps during the open states. The I- V relations showed rectification, such that current from the cis-side toward the trans-side is larger than that in the opposite direction. The intrinsic rectification is mainly attributed to the macro dipoles of parallel peptide helices surrounding a central pore.

Mg2+-dependent gating and strong inward rectification of the cation channel TRPV6.

TRPV6 (CaT1/ECaC2), a highly Ca2+-selective member of the TRP superfamily of cation channels, becomes permeable to monovalent cations in the absence of extracellular divalent cations. The monovalent currents display characteristic voltage-dependent gating and almost absolute inward rectification. Here, we show that these two features are dependent on the voltage-dependent block/unblock of the channel by intracellular Mg2+. Mg2+ blocks the channel by binding to a site within the transmembrane electrical field where it interacts with permeant cations. The block is relieved at positive potentials, indicating that under these conditions Mg2+ is able to permeate the selectivity filter of the channel. Although sizeable outward monovalent currents were recorded in the absence of intracellular Mg2+, outward conductance is still ∼10 times lower than inward conductance under symmetric, divalent-free ionic conditions. This Mg2+-independent rectification was preserved in inside-out patches and not altered by high intracellular concentrations of spermine, indicating that TRPV6 displays intrinsic rectification. Neutralization of a single aspartate residue within the putative pore loop abolished the Mg2+ sensitivity of the channel, yielding voltage-independent, moderately inwardly rectifying monovalent currents in the presence of intracellular Mg2+. The effects of intracellular Mg2+ on TRPV6 are partially reminiscent of the gating mechanism of inwardly rectifying K+ channels and may represent a novel regulatory mechanism for TRPV6 function in vivo.

The phytotoxic lipodepsipeptide syringopeptin 25A from Pseudomonas syringae pv syringae forms ion channels in sugar beet vacuoles.

Syringopeptin 25A (SP(25)A) belongs to a family of cyclic lipodepsipeptides (LDPs) produced by the gram-negative bacterium Pseudomonas syringae, a phytopathogenic organism that affects several plants of agronomic interest. LDPs increase the permeability of plasma and, possibly, intracellular membranes in plant cells. Consistently, SP(25)A forms ion channels in planar lipid bilayers and other model membranes. Here we used sugar beet tonoplasts as a new biological model system to study toxin action. When applied to the vacuoles by a fast perfusion procedure, SP(25)A increases membrane permeability by forming discrete ion channels even at low applied potentials. The SP(25)A channel displays anion selectivity (with a Cl-/K+ permeability ratio of 6.7 +/- 1.3) and has intrinsic rectification properties that derive from a different channel conductance at negative and positive voltages, presumably owing to an asymmetric distribution of fixed charges on the pore. Substitution of chloride with different anions reveals the following selectivity sequence NO3- approximately Cl-> F- > gluconate-, suggesting that the permeation pore is filled with water. The properties of the SP(25)A channels in vacuolar membranes are similar to those observed in planar lipid membranes prepared with asolectin. This work provides a direct demonstration of toxin effects on a native plant membrane, extending to a biological system previous results obtained on artificial planar lipid membranes.

Design and synthesis of light-harvesting rods for intrinsic rectification of the migration of excited-state energy and ground-state holesElectronic supplementary information (ESI) available: 1H and 13C NMR spectra for all new porphyrin precursors; 1H NMR and LD-MS spectra for all new porphyrins and porphyrin arrays (LD-MS only for deprotected arrays 12′ and 14′, and pentad 18); analytical SEC data for all

We present the design of molecular materials for ultimate use in solid-state solar cells. The molecular materials are semi-rigid oligomeric rods of defined length with metalloporphyrins in the backbone and a carboxy group at one end for attachment to a surface. The rods are designed to absorb visible light, and then undergo excited-state energy transfer and ground-state hole transfer in opposite directions along the length of the rod. The rational synthesis of the multiporphyrin arrays relies on joining porphyrin building blocks in an efficient and controlled manner. Several porphyrin building blocks have been synthesized that bear bromophenyl, iodophenyl, trimethylsilylethynylphenyl and/or ethynylphenyl substituents for use in a copper-free Sonogashira reaction using Pd2(dba)3 and P(o-tol)3. Competition experiments performed on equimolar quantities of an iodo-porphyrin and a bromo-porphyrin with an ethynyl-porphyrin show iodo + ethyne coupling with a low amount (35 °C) or undetectable amount (22 °C) of bromo + ethyne coupling. Efficient coupling of bromo-porphyrins with ethynyl-porphyrins was achieved using the same copper-free Sonogashira reaction conditions at higher temperature (50 °C or 80 °C). These findings allow successive coupling reactions to be achieved using substrates bearing iodo and bromo synthetic handles. Thus, a porphyrin-based tetrad (or pentad) was synthesized with a final convergent coupling of a bromo-substituted dyad (or triad) and an ethynyl-substituted dyad. A porphyrin triad was prepared by sequential iodo + ethyne coupling reactions. The triad, tetrad, and pentad each are comprised of a terminal magnesium porphyrin bearing one carboxy group (for surface attachment) and two pentafluorophenyl groups; the remaining porphyrins in each array are present as the zinc chelate. Electrochemical characterization of benchmark porphyrins indicates the presence of the desired electrochemical gradient for hole hopping in the arrays. Static absorption data indicate that the arrays are weakly coupled, while static fluorescence data indicate that the excited-state energy flows in high yield to the terminal magnesium porphyrin. Time-resolved spectroscopic analysis leads to rate constants in THF of (9 ps)−1, (15 ps)−1, and (30 ps)−1 for ZnMg dyad 20, Zn2Mg triad 13, and Zn3Mg tetrad 15, respectively, and quantum efficiencies ≥99% for energy flow to the magnesium porphyrin in each case. These design and synthesis strategies should be useful for the construction of materials for molecular-based solar cells.

Interactions of polyamines with ion channels.

Endogenous polyamines, in particular spermine, have been found to cause block and modulation of a number of types of ion channel. Intracellular spermine is responsible for intrinsic gating and rectification of strong inward rectifier K+ channels by directly plugging the ion channel pore. These K+ channels control the resting membrane potential in both excitable and non-excitable cells, and control the excitability threshold in neurons and muscle cells. Intracellular spermine causes inward rectification at some subtypes of Ca2+-permeable glutamate receptors in the central nervous system, again by plugging the receptor channel pore, and spermine can even permeate the ion channel of these receptors. Extracellular spermine has multiple effects at the N-methyl-d-aspartate (NMDA) subtype of glutamate receptor, including stimulation that increases the size of NMDA receptor currents, and voltage-dependent block. A number of polyamine-conjugated arthropod toxins and synthetic polyamine analogues are potent antagonists of glutamate receptors, and represent new tools with which to study these receptors. Interactions of polyamines with other types of cation channels have been reported. This area of research represents a new biology and a new pharmacology of polyamines.

Inward rectification of the IRK1 K+ channel reconstituted in lipid bilayers

Inwardly rectifying potassium (K+) channels (IRK1) were incorporated into lipid bilayers to test the relative contributions of various mechanisms to inward rectification. IRK1 channels were expressed in Xenopus laevis oocytes and oocyte membrane vesicles containing the channels were fused with lipid bilayers. The major properties of the IRK1 channel were similar whether measured in the oocyte membrane or lipid bilayer; the single channel conductance was 21 pS in 140 mM symmetrical [K+] and varied as a square root of external [K+]. Importantly, IRK1 channels display voltage-dependent inward rectification in the absence of divalent ions or charged regulators such as spermine, indicating that they possess an intrinsic rectification mechanism. Although rectification was significantly increased by either Mg2+ or spermine added to the cytoplasmic face of the channel, their effects could not be explained by simple block of the open pore. The Hille and Schwartz (1978) model, originally proposed to explain inward rectification by singly charged blocking particles, cannot be used to explain rectification by multiply charged blocking particles. As an alternative, we propose that in addition to a slow gating mechanism producing long lasting open and closed states, there is a distinct, intrinsic fast gating process amplified by cytoplasmic Mg2+ and/or polyamine binding to the channel.

Small-conductance chloride channels in human peripheral T lymphocytes

During whole-cell patch-clamp recording from normal (nontransformed) human T lymphocytes a chloride current spontaneously activated in > 98% of cells (n > 200) in the absence of applied osmotic or pressure gradients. However, some volume sensitivity was observed, as negative pressure pulses reduced the current. With iso-osmotic bath and pipette solutions the peak amplitude built up (time constant approximately 23 sec at room temperature), a variable-duration plateau phase followed, then the current ran down spontaneously (time constant approximately 280 sec). The anion permeability sequence, calculated from reversal potentials was I-, Br- > NO3-, Cl- > CH3SO3-, HCO3- > CH3COO- > F- > aspartate, gluconate, SO4(2-) and there was no measurable monovalent cation permeability. The Cl- current was independent of time during long voltage steps and there was no evidence of voltage-dependent gating; however, the current showed intrinsic outward rectification in symmetrical Cl- solutions. The conductance of the channels underlying the whole-cell current was calculated from fluctuation analysis, using power-spectral density and variance-vs.-mean analysis. Both methods yielded a single channel conductance of about 0.6 pS at -70 mV (close to the normal resting potential of T lymphocytes). The power spectral density function was best fit by the sum of two Lorentzian functions, with corner frequencies of 30 and 295 Hz, corresponding to mean open times of 0.54 and 5.13 msec. The pharmacological profile included rapid block by external application of flufenamic acid (50 microM), 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB, 100 microM), [6,7-dichloro-2-cyclopentyl-2,3- dihydro-2-methyl-1-oxo-1H-inden-5-yl)oxy] acetic acid (IAA-94, 250 microM) or 100 microM 1,9-dideoxyforskolin. The stilbene derivatives DIDS (4,4'-diisothiocyano-2,2' disulphonic acid stilbene, 500 microM) and SITS (4-acetamido-4'-isothiocyano-2,2'-disulphonic acid stilbene, 500 microM) prevented buildup of Cl- current after a 30-min preincubation at 500 microM. When tested in a mitogenic assay, DIDS, flufenamic acid, NPPB and IAA-94 all inhibited T-cell proliferation, suggesting a physiological function in addition to the observed volume sensitivity.

Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification.

Inwardly rectifying potassium channels conduct ions more readily in the inward than the outward direction, an essential property for normal electrical activity. Although voltage-dependent block by internal magnesium ions may underlie inward rectification in some channels, an intrinsic voltage-dependent closure of the channel plays a contributory, or even exclusive, role in others. Here we report that, rather than being intrinsic to the channel protein, so-called intrinsic rectification of strong inward rectifiers requires soluble factors that are not Mg2+ and can be released from Xenopus oocytes and other cells. Biochemical and biophysical characterization identifies these factors as polyamines (spermine, spermidine, putrescine and cadaverine). The results suggest that intrinsic rectification results from voltage-dependent block of the channel pore by polyamines, not from a voltage sensor intrinsic to the channel protein.