Proton Sensitivity Research Articles

PH Modulation of Voltage-Gated Sodium Channels.

Changes in blood and tissue pH accompany physiological and pathophysiological conditions including exercise, cardiac ischemia, ischemic stroke, and cocaine ingestion. These conditions are known to trigger the symptoms of electrical diseases in patients carrying sodium channel mutations. Protons cause a diverse set of changes to sodium channel gating, which generally lead to decreases in the amplitude of the transient sodium current and increases in the fraction of non-inactivating channels that pass persistent currents. These effects are shared with disease-causing mutants in neuronal, skeletal muscle, and cardiac tissue and may be compounded in mutants that impart greater proton sensitivity to sodium channels, suggesting a role of protons in triggering acute symptoms of electrical disease.In this chapter, we review the mechanisms of proton block of the sodium channel pore and a suggested mode of action by which protons alter channel gating. We discuss the available data on isoform specificity of proton effects and tissue level effects. Finally, we review the role that protons play in disease and our own recent studies on proton-sensitizing mutants in cardiac and skeletal muscle sodium channels.

Characterization of CcSTOP1; a C2H2-type transcription factor regulates Al tolerance gene in pigeonpea.

Al-responsive citrate-transporting CcMATE1 function and its regulation by CcSTOP1 were analyzed using NtSTOP1 -KD tobacco- and pigeonpea hairy roots, respectively, CcSTOP1 binding sequence of CcMATE1 showed similarity with AtALMT1 promoter. The molecular mechanisms of Aluminum (Al) tolerance in pigeonpea (Cajanus cajan) were characterized to provide information for molecular breeding. Al-inducible citrate excretion was associated with the expression of MULTIDRUGS AND TOXIC COMPOUNDS EXCLUSION (CcMATE1), which encodes a citrate transporter. Ectopic expression of CcMATE1-conferred Al tolerance to hairy roots of transgenic tobacco with the STOP1 regulation system knocked down. This gain-of-function approach clearly showed CcMATE1 was involved in Al detoxification. The expression of CcMATE1 and another Al-tolerance gene, ALUMINUM SENSITIVE 3 (CcALS3), was regulated by SENSITIVE TO PROTON RHIZOTOXICITY1 (CcSTOP1) according to loss-of-function analysis of pigeonpea hairy roots in which CcSTOP1 was suppressed. An in vitro binding assay showed that the Al-responsive CcMATE1 promoter contained the GGNVS consensus bound by CcSTOP1. Mutation of GGNVS inactivated the Al-inducible expression of CcMATE1 in pigeonpea hairy roots. This indicated that CcSTOP1 binding to the promoter is critical for CcMATE1 expression. The STOP1 binding sites of both the CcMATE1 and AtALMT1 promoters contained GGNVS and a flanking 3' sequence. The GGNVS region was identical in both CcMATE1 and AtALMT1. By contrast, the 3' flanking sequence with binding affinity to STOP1 did not show similarity. Putative STOP1 binding sites with similar structures were also found in Al-inducible MATE and ALMT1 promoters in other plant species. The characterized Al-responsive CcSTOP1 and CcMATE1 genes will help in pigeonpea breeding in acid soil tolerance.

Photochemical and DFT/TD-DFT study of trifluoroethoxy substituted asymmetric metal-free and copper(II) phthalocyanines

Peripherally 2,2,2-trifluoroethoxy substituted asymmetric metal-free(3), and copper(II) (4) phthalocyanine (Pc) derivatives were synthesized and characterized by elemental analyses, IR spectra, 1H, 13C NMR and 19F NMR spectra, electronic spectra and mass spectra. All the Pcs 3 & 4 showed enhanced solubility in various organic solvents. The absorption spectra showed monomeric behavior evidenced by a single (narrow between 680 and 750 nm) Q band, for Pcs in different solvents. The aggregation behavior of Pcs was investigated at different concentrations in chloroform and Pcs were found to exist in non-aggregated form. The fluorescence behavior of the Pcs 3 & 4 was studied in chloroform. The phthalocyanine compounds are more fluorescent indicated that the potential of the compounds as photosensitizers in applications of PDT where singlet oxygen is required. An interesting feature of these compounds is the high proton sensitivity that comes out with the trace amount of acid present in solvents. The substituted Pc 3 and 4 showed similar stability in THF during photodegradation studies.

Transcriptional Regulation of Aluminum-Tolerance Genes in Higher Plants: Clarifying the Underlying Molecular Mechanisms.

Aluminum (Al) rhizotoxicity is one of the major environmental stresses that decrease global food production. Clarifying the molecular mechanisms underlying Al tolerance may contribute to the breeding of Al-tolerant crops. Recent studies identified various Al-tolerance genes. The expression of these genes is inducible by Al. Studies of the major Arabidopsis thaliana Al-tolerance gene, ARABIDOPSIS THALIANA ALUMINUM-ACTIVATED MALATE TRANSPORTER 1 (AtALMT1), which encodes an Al-activated malate transporter, revealed that the Al-inducible expression is regulated by a SENSITIVE TO PROTON RHIXOTOXICITY 1 (STOP1) zinc-finger transcription factor. This system, which involves STOP1 and organic acid transporters, is conserved in diverse plant species. The expression of AtALMT1 is also upregulated by several phytohormones and hydrogen peroxide, suggesting there is crosstalk among the signals involved in the transcriptional regulation of AtALMT1. Additionally, phytohormones and reactive oxygen species (ROS) activate various transcriptional responses, including the expression of genes related to increased Al tolerance or the suppression of root growth under Al stress conditions. For example, Al suppressed root growth due to abnormal accumulation of auxin and cytokinin. It activates transcription of TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS 1 and other phytohormone responsive genes in distal transition zone, which causes suppression of root elongation. On the other hand, overexpression of Al inducible genes for ROS-detoxifying enzymes such as GLUTATHIONE–S-TRANSFERASE, PEROXIDASE, SUPEROXIDE DISMUTASE enhances Al resistance in several plant species. We herein summarize the complex transcriptional regulation of an Al-inducible genes affected by STOP1, phytohormones, and ROS.

Limits of Resolution and Sensitivity of Proton Detected MAS Solid-State NMR Experiments at 111 kHz in Deuterated and Protonated Proteins

MAS solid-state NMR is capable of determining structures of protonated solid proteins using proton-detected experiments. These experiments are performed at MAS rotation frequency of around 110 kHz, employing 0.5 mg of material. Here, we compare 1H, 13C correlation spectra obtained from protonated and deuterated microcrystalline proteins at MAS rotation frequency of 111 kHz, and show that the spectral quality obtained from deuterated samples is superior to those acquired using protonated samples in terms of resolution and sensitivity. In comparison to protonated samples, spectra obtained from deuterated samples yield a gain in resolution on the order of 3 and 2 in the proton and carbon dimensions, respectively. Additionally, the spectrum from the deuterated sample yields approximately 2–3 times more sensitivity compared to the spectrum of a protonated sample. This gain could be further increased by a factor of 2 by making use of stereospecific precursors for biosynthesis. Although the overall resolution and sensitivity of 1H, 13C correlation spectra obtained using protonated solid samples with rotation frequencies on the order of 110 kHz is high, the spectral quality is still poor when compared to the deuterated samples. We believe that experiments involving large protein complexes in which sensitivity is limiting will benefit from the application of deuteration schemes.

Malate-dependent Fe accumulation is a critical checkpoint in the root developmental response to low phosphate

Low phosphate (Pi) availability constrains plant development and seed production in both natural and agricultural ecosystems. When Pi is scarce, modifications of root system architecture (RSA) enhance the soil exploration ability of the plant and lead to an increase in Pi uptake. In Arabidopsis, an iron-dependent mechanism reprograms primary root growth in response to low Pi availability. This program is activated upon contact of the root tip with low-Pi media and induces premature cell differentiation and the arrest of mitotic activity in the root apical meristem, resulting in a short-root phenotype. However, the mechanisms that regulate the primary root response to Pi-limiting conditions remain largely unknown. Here we report on the isolation and characterization of two low-Pi insensitive mutants (lpi5 and lpi6), which have a long-root phenotype when grown in low-Pi media. Cellular, genomic, and transcriptomic analysis of low-Pi insensitive mutants revealed that the genes previously shown to underlie Arabidopsis Al tolerance via root malate exudation, known as SENSITIVE TO PROTON RHIZOTOXICITY (STOP1) and ALUMINUM ACTIVATED MALATE TRANSPORTER 1 (ALMT1), represent a critical checkpoint in the root developmental response to Pi starvation in Arabidopsis thaliana Our results also show that exogenous malate can rescue the long-root phenotype of lpi5 and lpi6 Malate exudation is required for the accumulation of Fe in the apoplast of meristematic cells, triggering the differentiation of meristematic cells in response to Pi deprivation.

Proton detection of MAS solid-state NMR spectra of half-integer quadrupolar nuclei

Fast magic angle spinning (MAS) and proton detection has found widespread application to enhance the sensitivity of solid-state NMR experiments with spin-1/2 nuclei such as 13C, 15N and 29Si, however, this approach is not yet routinely applied to half-integer quadrupolar nuclei. Here we have investigated the feasibility of using fast MAS and proton detection to enhance the sensitivity of solid-state NMR experiments with half-integer quadrupolar nuclei. The previously described dipolar hetero-nuclear multiple quantum correlation (D-HMQC) and dipolar refocused insensitive nuclei enhanced by polarization transfer (D-RINEPT) pulse sequences were used for proton detection of half-integer quadrupolar nuclei. Quantitative comparisons of signal-to-noise ratios and the sensitivity of proton detected D-HMQC and D-RINEPT and direct detection spin echo and quadrupolar Carr-Purcell Meiboom-Gill (QCPMG) solid-state NMR spectra, demonstrate that one dimensional proton detected experiments can provide sensitivity similar to or exceeding that obtainable with direct detection QCPMG experiments. 2D D-HMQC and D-RINEPT experiments provide less sensitivity than QCPMG experiments but proton detected 2D hetero-nuclear correlation solid-state NMR spectra of half-integer nuclei can still be acquired in about the same time as a 1D spin echo spectrum. Notably, the rarely used D-RINEPT pulse sequence is found to provide similar, or better sensitivity than D-HMQC in some cases. Proton detected D-RINEPT benefits from the short longitudinal relaxation times (T1) normally associated with half-integer quadrupolar nuclei, it can be combined with existing signal enhancement methods for quadrupolar nuclei, and t1-noise in the indirect dimension can easily be removed by pre-saturation of the 1H nuclei. The rapid acquisition of proton detected 2D HETCOR solid-state NMR spectra of a range of half-integer quadrupolar nuclei such as 17O, 27Al, 35Cl and 71Ga is demonstrated.

Single event effects sensitivity of low energy proton in Xilinx Zynq-7010 system-on chip

In this paper, experimental methods are emphatically described for measuring the proton single event effects (SEE) in Xilinx Zynq-7010 system-on chip. Experimental data are presented showing that low energy (3MeV≤Energy≤10MeV) proton irradiation can cause single event effects in different hardware blocks of Xilinx Zynq-7010 SoC, including D-Cache, programmable logic (PL), arithmetic logical unit (ALU), float point unit (FPU) and direct memory access (DMA). Moreover, the sensitivities of different hardware blocks to single event effects are different. Finally, the Stopping and Range of Ions in Matter (SRIM) software calculations show the possible reasons for this difference.

Trap Design and Construction for High-Power Multinuclear Magnetic Resonance Experiments.

Performing multinuclear experiments requires one or more radiofrequency (RF) coils operating at both the proton and second-nucleus frequencies; however, inductive coupling between coils must be mitigated to retain proton sensitivity and coil tuning stability. The inclusion of trap circuits simplifies placement of multinuclear RF coils while maintaining inter-element isolation. Of the commonly investigated non-proton nuclei, perhaps the most technically demanding is carbon-13, particularly when applying a proton decoupling scheme to improve the resulting spectra. This work presents experimental data for trap circuits withstanding high-power broadband proton decoupling of carbon-13 at 7 T. The advantages and challenges of building trap circuits with various inductor and capacitor components are discussed. Multiple trap designs are evaluated on the bench and utilized on an RF coil at 7 T to detect broadband proton-decoupled carbon-13 spectra from a lipid phantom. A particular trap design, built from a coaxial stub inductor and high-voltage ceramic chip capacitors, is highlighted owing to both its performance and adaptability for planar array coil elements with diverse spatial orientations.

Detailed Analysis of the Binding Mode of Vanilloids to Transient Receptor Potential Vanilloid Type I (TRPV1) by a Mutational and Computational Study.

Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel and a multimodal sensor protein. Since the precise structure of TRPV1 was obtained by electron cryo-microscopy, the binding mode of representative agonists such as capsaicin and resiniferatoxin (RTX) has been extensively characterized; however, detailed information on the binding mode of other vanilloids remains lacking. In this study, mutational analysis of human TRPV1 was performed, and four agonists (capsaicin, RTX, [6]-shogaol and [6]-gingerol) were used to identify amino acid residues involved in ligand binding and/or modulation of proton sensitivity. The detailed binding mode of each ligand was then simulated by computational analysis. As a result, three amino acids (L518, F591 and L670) were newly identified as being involved in ligand binding and/or modulation of proton sensitivity. In addition, in silico docking simulation and a subsequent mutational study suggested that [6]-gingerol might bind to and activate TRPV1 in a unique manner. These results provide novel insights into the binding mode of various vanilloids to the channel and will be helpful in developing a TRPV1 modulator.

Comparison of kinetic and pharmacological profiles of recombinant α1γ2L and α1β2γ2L GABAA receptors – A clue to the role of intersubunit interactions

The fastest inhibitory mechanism in the CNS is mediated by ionotropic GABAA receptors and it is known that subunit composition critically determines their properties. While a typical GABAA receptor consists of two α, two β and one γ/δ subunit, there are some exceptions, e.g. αβ receptors. Functional α1γ2 GABAA receptors can be expressed in recombinant model (Verdoorn et al., 1990) and although their role remains unknown, it seems appealing to extend their characterization to further explore the structure-function relationship of GABAA receptors. Intriguingly, this receptor is lacking canonical GABA binding sites but it can be activated by GABA and dose-response relationships for α1β2γ2L and α1γ2L receptors overlap. Deactivation kinetics was similar for both receptors but the percentage of the fast component was smaller in the case of α1γ2L receptors and, consequently, the mean deactivation time constant was slower. The rate and extent of macroscopic desensitization were smaller in the case of α1γ2L receptors but they showed slower recovery. Both receptor types had a similar proton sensitivity showing only subtle but significant differences in pH effects on deactivation. Flurazepam exerted a similar effect on both receptors but the rapid deactivation components were differently affected and an opposite effect was observed on desensitization extent. Rebound currents evoked by pentobarbital were undistinguishable for both receptor types. Taking altogether, although some significant differences were found, α1β2γ2L and α1γ2L receptors showed unforeseen similarity. We propose that functioning of GABAA receptors might rely on subunit-subunit cooperative interactions to a larger extent than believed so far.

Heteromerization of G2A and OGR1 enhances proton sensitivity and proton-induced calcium signals

Proton-sensing G-protein-coupled receptors (GPCRs; OGR1, GPR4, G2A, TDAG8), with full activation at pH 6.4 ∼ 6.8, are important to pH homeostasis, immune responses and acid-induced pain. Although G2A mediates the G13-Rho pathway in response to acid, whether G2A activates Gs, Gi or Gq proteins remains debated. In this study, we examined the response of this fluorescence protein-tagged OGR1 family to acid stimulation in HEK293T cells. G2A did not generate detectable intracellular calcium or cAMP signals or show apparent receptor redistribution with moderate acid (pH ≥ 6.0) stimulation but reduced cAMP accumulation under strong acid stimulation (pH ≤ 5.5). Surprisingly, coexpression of OGR1- and G2A-enhanced proton sensitivity and proton-induced calcium signals. This alteration is attributed to oligomerization of OGR1 and G2A. The oligomeric potential locates receptors at a specific site, which leads to enhanced proton-induced calcium signals through channels.

Elucidating Proton Sensitivity and Activation in the Gloeobacter Violaceus Ligand-Gated Ion Channel

The pentameric ligand-gated ion channel (pLGIC) family plays an important role in the chemical-to-electrical transduction of neuronal signaling. Although human pLGICs are endogenously activated by acetylcholine, serotonin, zinc, glycine, or gamma-aminobutyric acid, some of them notably glycine and gamma-aminobutyric acid receptors are modulated by protons. The Gloeobacter violaceus ligand-gated ion channel (GLIC) is a prokaryotic proton-gated ion channel of the family and was the first pLGIC to be structurally resolved in both an open and closed conformation offering a structural perspective to the mechanism of activation for the pLGIC family. Determining the proton modulatory site(s) of receptors, including acid-sensing and ATP-sensitive K+ channels, may be a complicated endeavor. Although residues have been identified in these receptors as key proton-sensitive sites the underlying molecular mechanism of modulation is not always clear. GLIC has been shown to be a robust model of the pLGIC family, and understanding how a single or several proton(s) can stabilize the open conformation would shed light on the intricate mechanism involved in channel opening of human pLGICs. This comprehension might also pave the way to reveal proton modulatory mechanisms of other receptors. Here we represent a systematic functional evaluation of titratable residues in GLIC to pinpoint the key proton sensitive sites that play a role in the extracellular initiation of the activation mechanism. We have found two key inter-subunit interacting regions, distinct from the ligand-binding pocket, which play key roles in the opening of the channel.

Chemical consequences of pyrazole orientation in Ru(II) complexes of unsymmetric quinoline-pyrazole ligands.

A series of homoleptic Ru(II) complexes including the tris-bidentate complexes of a new bidentate ligand 8-(1-pyrazol)-quinoline (Q1Pz) and bidentate 8-(3-pyrazol)-quinoline (Q3PzH), as well as the bis-tridentate complex of bis(quinolinyl)-1,3-pyrazole (DQPz) was studied. Together these complexes explore the orientation of the pyrazole relative to the quinoline. By examining the complexes structurally, photophysically, photochemically, electrochemically, and computationally by DFT and TD-DFT, it is shown that the pyrazole orientation has a significant influence on key properties. In particular, its orientation has noticeable effects on oxidation and reduction potentials, photostability and proton sensitivity, indicating that [Ru(Q3PzH)3](2+) is a particularly good local environment acidity-probe candidate.

Single event upsets sensitivity of low energy proton in nanometer static random access memory

Low-energy protons are able to generate enough energy through direct ionization to cause a high single event upset cross section as the feature size of semiconductor devices shrinks. It poses a large challenge on the present proton single event modeling test technique and the space upset rate prediction method. Experimental study of proton single event effect in three different feature sizes of static random access memory (SRAM) (i.e. 65 nm, 90 nm, and 250 nm) is carried out based on domestic low-energy proton accelerators and also the foreign middle-high proton accelerators. Complete cross section curves of proton single event upset from low energy to high energy are acquired. Test results show that single event upset cross section below 1 MeV proton is up to three orders of magnitude higher than the saturation cross section of high-energy proton in nanometer SRAM. However, single event upset is not observed for protons below 3 MeV in 250 nm SRAM, and no single event multiple-cell upsets occur for protons below 1 MeV in 90 nm and 65 nm SRAM. The accurate geometrical structure model of composite sensitive volume is constructed through the combination of test data with device information, and calibrated further by single event test data of low-LET heavy ion and high-energy proton. Simulation results based on the model and Monte-Carlo calculation can reveal the root cause of low-proton single event upset cross section peak. Proton single event upsets are only caused through direct ionization of protons below 1 MeV. When low-energy protons pass through the multiple metallization and passivation layers of the device, the energy spectrum is broadened near the Bragg peak of the proton direct ionization, and the energy is deposited concentratedly into the sensitive volume through direct ionization. When the proton energy is too high or too low, the energy can not be deposited effectively into the sensitive volume through direct ionization. The energy spectrum straggling of low-energy protons due to the use of degrader has a large influence on the height and width of the single event upset cross section peak. Moreover, the contribution of low protons to the space proton single event upset rate is predicted for GEO orbit environment in the worst day environment. It shows that the direct ionization from low energy dominates the proton single event upset rate in the space in 65 nm SRAM. With the development of device technology, the critical charge of single event upset will be further reduced; and to the single event upset from low proton direct ionization more attention must be paid in the study and evaluation of single event effect.

Determination of F, Na, Mg, Al and P in Indian tea powders by a proton induced γ-ray emission technique

The high sensitivity of proton induced γ-ray emission technique to light elements is exploited to determine F, Na, Mg, Al and P in several Indian tea powders.

Miniaturized Ir/IrOx pH Sensor for Quantitative Diagnosis of Dental Caries

Diagnosis of dental caries is one of the most basic skills for oral healthcare professionals; however, the detection methods are based on visually diagnosis, such as inspection, palpation, and X-ray imaging. Therefore, quantitative and objective diagnostic technique is needed [1]. The aim of this study is fabrication and evaluation of Iridium/Iridium Oxide (Ir/IrOx) pH sensor for quantitative diagnosis of dental caries. The potentiometric response to pH showed -57.4mV/pH in evaluated pH range from 4 to 8, which demonstrated that our electrode possesses the excellent proton sensitivity (Nernst slope; -59.2mV/pH). Based on the evaluation results of dental caries, we confirmed the possibility for quantitative diagnosis of dental caries using Ir/IrOx electrode based on the pH as an index.

Proton observed phosphorus editing (POPE) for in vivo detection of phospholipid metabolites.

The purpose of this article was to compare the sensitivity of proton observed phosphorus editing (POPE) with direct (31) P MRS with Ernst angle excitation for (1) H-(31) P coupled metabolites at 7 T. POPE sequences were developed for detecting phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC), and glycerophosphoethanolamine (GPE) on the (1) H channel, thereby using the enhanced sensitivity of the (1) H nuclei over (31) P detection. Five healthy volunteers were examined with POPE and (31) P-MRS. POPE editing showed a more than doubled sensitivity in an ideal phantom experiment as compared with direct (31) P MRS with Ernst angle excitation. In vivo, despite increased relaxation losses, significant gains in signal-to-noise ratio (SNR) of 30-40% were shown for PE and GPE + PC levels in the human brain. The SNR of GPC was lower in the POPE measurement compared with the (31) P-MRS measurement. Furthermore, selective narrowband editing on the (31) P channel showed the ability to separate the overlapping GPE and PE signals in the (1) H spectrum. POPE can be used for enhanced detection of (1) H-(31) P coupled metabolites in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

Characterization of Imidazopyridine Compounds as Negative Allosteric Modulators of Proton-Sensing GPR4 in Extracellular Acidification-Induced Responses.

G protein-coupled receptor 4 (GPR4), previously proposed as the receptor for sphingosylphosphorylcholine, has recently been identified as the proton-sensing G protein-coupled receptor (GPCR) coupling to multiple intracellular signaling pathways, including the Gs protein/cAMP and G13 protein/Rho. In the present study, we characterized some imidazopyridine compounds as GPR4 modulators that modify GPR4 receptor function. In the cells that express proton-sensing GPCRs, including GPR4, OGR1, TDAG8, and G2A, extracellular acidification stimulates serum responsive element (SRE)-driven transcriptional activity, which has been shown to reflect Rho activity, with different proton sensitivities. Imidazopyridine compounds inhibited the moderately acidic pH-induced SRE activity only in GPR4-expressing cells. Acidic pH-stimulated cAMP accumulation, mRNA expression of inflammatory genes, and GPR4 internalization within GPR4-expressing cells were all inhibited by the GPR4 modulator. We further compared the inhibition property of the imidazopyridine compound with psychosine, which has been shown to selectively inhibit actions induced by proton-sensing GPCRs, including GPR4. In the GPR4 mutant, in which certain histidine residues were mutated to phenylalanine, proton sensitivity was significantly shifted to the right, and psychosine failed to further inhibit acidic pH-induced SRE activation. On the other hand, the imidazopyridine compound almost completely inhibited acidic pH-induced action in mutant GPR4. We conclude that some imidazopyridine compounds show specificity to GPR4 as negative allosteric modulators with a different action mode from psychosine, an antagonist susceptible to histidine residues, and are useful for characterizing GPR4-mediated acidic pH-induced biological actions.

POES MEPED differential flux retrievals and electron channel contamination correction

AbstractA correction method to remove proton contamination from the electron channels of the Polar‐orbiting Operational Environmental Satellites Medium Energy Proton/Electron Detector (MEPED) is described. Proton contamination estimates are based on measurements in five of the MEPED proton spectral channels. A constrained inversion of the MEPED proton channel response function matrix is used to calculate proton differential flux spectra. In this inversion, the proton energy distribution is described by a weighted combination of exponential, power law, and Maxwellian distributions. Proton contamination in the MEPED electron spectral channels is derived by applying the electron channel proton sensitivities to the proton fluxes from the best fit proton spectra. Once the electron channel measurements are corrected for proton contamination, an inversion of the electron channel response function matrix is used to calculate electron differential flux spectra. A side benefit of the method is that it yields an estimate for the integrated electron flux in the energy range from 300 keV to 2.5 MeV with a center energy at ~800 keV. The final product is a differential spectrum of electron flux covering the energy range from about 10 keV to 2.5 MeV that is devoid of proton contamination except during large solar proton events. Comparisons of corrected MEPED differential fluxes to the Detection of Electromagnetic Emissions Transmitted from Earthquake Regions Instrument for Detecting Particles show that MEPED fluxes are greater than what is expected from altitude‐induced particle population changes; this is attributed at least partially to measurement differences in pitch angle range.