Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Protons”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,567 records · Page 87Linked to original sources
PubMed2006

Nocturnal acid breakthrough in children with reflux esophagitis taking proton pump inhibitors.

OBJECTIVES: We aimed to determine if nocturnal acid breakthrough occurs in children receiving proton pump inhibitors for reflux esophagitis, and to compare the healing of esophagitis in children with nocturnal acid breakthrough receiving proton pump inhibitors +/- ranitidine. METHODS: This is a prospective, double-blind study. Endoscopic and histologic esophagitis were scored 0-4 and 0-3, respectively. Patients were treated with a proton pump inhibitor twice daily and esophagogastric pH monitoring was performed at week 3. Patients with nocturnal acid breakthrough were randomized. One group received ranitidine and the other received placebo at bedtime in addition to proton pump inhibitor therapy. Endoscopy was performed on all patients (with pH monitoring on patients with nocturnal acid breakthrough) during the 17th week of therapy. RESULTS: We enrolled 18 patients, ages 1 to 13 years (mean = 10.3 years). Mean baseline endoscopic and histologic scores were 3.1 +/- 1.4 and 1.8 +/- 0.7, respectively. Mean dose of proton pump inhibitor was 1.3 mg/kg +/- 0.6. Nocturnal acid breakthrough was documented in 16/18 (89%) patients. Seven patients received ranitidine and 9 received placebo. The reflux index improved: mean of 14.3 at baseline, 2.0 at week 3 (P = 0.0001), and 5.1 at week 17 (P = 0.09). Nocturnal acid breakthrough persisted in 9/12 (75%) patients, 3 of whom received ranitidine at bedtime. Esophagitis improved in all patients following therapy: mean endoscopy and histology scores were 1.6 +/- 1.8 (P = 0.0020) and 0.8 +/- 0.9 (P = 0.0013), respectively. Symptoms significantly improved from a mean score of 2.0 at baseline to 0.4 at week 17 (P = 0.0001). CONCLUSIONS: Nocturnal acid breakthrough is common in pediatric patients treated with proton pump inhibitors. Reflux index remains normal in spite of nocturnal acid breakthrough. Symptoms and esophagitis continued to improve during therapy in spite of nocturnal acid breakthrough. There appears to be no additional benefit to supplementation with ranitidine at bedtime.

Adolescent↗
PubMed1995

Immunocytological localization of an epitope-tagged plasma membrane proton pump (H(+)-ATPase) in phloem companion cells.

In higher plants, the plasma membrane proton pump (H(+)-ATPase) is encoded by a surprisingly large multigene family whose members are expressed in different tissues. Using an 18-amino acid epitope tag derived from the animal oncogene c-Myc, we have performed immunocytolocalization measurements of the protein expressed by one member of this family, AHA3 (Arabidopsis H(+)-ATPase isoform 3). Immunofluorescence studies with tissue sections of transgenic plants have revealed that c-Myc-tagged AHA3 is restricted to the plasma membrane of phloem companion cells, whereas other AHA isoproteins are more widely distributed in the plasma membrane of other cell types. Electron microscopy with immunogold-labeled tissue sections suggests that there is a high concentration of proton pumps in the plasma membrane of companion cells but a much lower concentration in the plasma membrane of sieve elements. Due to plasmodesmata connecting the plasma membrane of these two adjacent cell types, it is likely that the proton motive force generated by the proton pump in companion cells can serve to power the uptake of sugar by proton-coupled symporters in either the companion cell or sieve element cell. The abundance of the proton pump in the plasma membrane of companion cells supports an apoplastic model for phloem loading in which the metabolic energy that drives sugar uptake is consumed by AHA3 at the companion cell plasma membrane. These experiments with a genetically altered integral plasma membrane protein demonstrate the utility of using a short c-Myc sequence as an epitope tag in Arabidopsis. Furthermore, our results demonstrate that, using genes encoding individual members of a gene family, it is possible to label plasma membrane proteins immunologically in specific, differentiated cell types of higher plants.

Amino Acid Sequence↗
PubMed2004

Guidelines for the appropriate use of non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2-specific inhibitors and proton pump inhibitors in patients requiring chronic anti-inflammatory therapy.

AIM: To rationalize decision making around the use of different non-steroidal anti-inflammatory drug (NSAID) treatment strategies in patients with varying degrees of gastrointestinal and cardiovascular risk. METHODS: The panel comprised nine physicians (three rheumatologists, two internists, two gastroenterologists and two cardiologists) from geographically diverse areas practising in community-based settings (n = 4) and academic institutions (n = 5). A literature review was performed by the authors on the risks, benefits and costs of NSAIDs, cyclo-oxygenase-2-specific inhibitors and proton pump inhibitor co-therapy. The RAND/UCLA Appropriateness Method was used to rate 304 clinical scenarios as 'appropriate', 'uncertain' or 'inappropriate'. RESULTS: In patients with no previous gastrointestinal event and not concurrently on aspirin (low risk), the panel rated the use of an NSAID alone as 'appropriate' for those aged < 65 years, and the use of an NSAID +proton pump inhibitor or cyclo-oxygenase-2-specific inhibitor + proton pump inhibitor as 'inappropriate'. For patients aged > 65 years and at low risk, an NSAID or cyclo-oxygenase-2-specific inhibitor alone was rated as 'uncertain'. For patients with a previous gastrointestinal event or who concurrently received aspirin, an NSAID alone was rated as 'inappropriate', and either a cyclo-oxygenase-2-specific inhibitor or an NSAID +proton pump inhibitor was rated as 'appropriate'. Finally, for patients with a previous gastrointestinal event and on aspirin, an NSAID or cyclo-oxygenase-2-specific inhibitor in conjunction with a proton pump inhibitor was rated as 'appropriate'. CONCLUSIONS: Clinicians and managed care entities need to balance the risks, benefits and costs of NSAIDs, cyclo-oxygenase-2-specific inhibitors and the prophylactic use of proton pump inhibitors. The guidelines given here can assist this process.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1981

Inhibition of the links between electron transfer and proton translocation in mitochondria.

The mechanism by which proton extrusion is linked to electron transfer in mitochondria was investigated by means of the primary amine-specific reagent fluorescamine, and of compounds obtained from the reaction of fluorescamine with simple amines (e.g. benzylamine) and with the mycosamine-containing antibiotic amphotericin B. The effect of these 'modifiers' (i.e. fluorescamine transfer chain were assayed separately using specific inhibitors to block the action associated with the other site. Both types of modifiers inhibited the proton extrusion across the membrane to a significantly greater extent than the electron transfer process in both sites II and III. In contrast, the lactone derivative (or cyclic form) of the amine-fluorescamine compounds had no significant inhibitory effect on the proton extrusion and its associated electron transfer. These results are consistent with the hypothesis that the link between proton extrusion and electron transfer in mitochondria is indirect in nature. The results show that: (a) the links involved in sites II and III are identical or very similar in nature; (b) a covalent modification of primary amino groups in the inner membrane is not essential for the expression of these differential inhibitory effects; (c) specific structural features in the amine-fluorescamine compounds, and in the mitochondria-fluorescamine derivatives, are crucial for the expression of the inhibitory effects. Our results contradict the 'redox loop' model of Mitchell, and are compatible with the proton pump concept for the linked proton translocation in oxidative phosphorylation.

Animals↗
PubMed1983

Determination of protonation sites in thermospermine and in some other polyamines by 15N and 13C nuclear magnetic resonance spectroscopy.

The pK values of thermospermine, a novel asymmetric tetraamine (4,8-diazadodecane-1,12-diamine), have been determined for the first time by the conventional titration method with subsequent data analyses. It was found to be the most basic polyamine among naturally occurring tetraamines. The 15N NMR titration method was applied to determine its protonation site. Natural-abundance 15N magnetic resonance spectra of the polyamine have been recorded as a function of pH from its free to the protonated form. Its apparent pK values, as well as the intrinsic chemical shifts for each stage of protonation, have been calculated from the NMR titration curve by using a nonlinear least-squares method. The four protonation sites of thermospermine have been successfully determined to be N12, N1, N-8, and N-4 in that order from the free to the completely protonated form. In a similar manner the protonation sites of spermidine and two symmetric tetraamines, thermine and spermine, have been established. 13C NMR experiments for the four polyamines were almost consistent with those of 15N NMR. Owing to the much higher concentration of the polyamines furnished for NMR titration experiments, the pK values obtained by NMR were larger than those derived by the conventional titration methods.

Binding Sites↗
PubMed1984

A high-resolution proton nuclear-magnetic-resonance investigation of carp hemoglobin. Conformational differences between carp and human normal adult hemoglobins in solution.

The high-resolution proton nuclear magnetic resonance spectra of carp hemoglobin have been compared to those of human normal adult hemoglobin. Carp deoxy and carbonmonoxy hemoglobins in the deoxy-type quaternary state exhibit two downfield exchangeable proton resonances as compared to four seen in human normal adult deoxyhemoglobin. This suggests that two of the hydrogen bonds present in human normal adult deoxyhemoglobin are absent or occur in very different environments in carp hemoglobin. One of the exchangeable proton resonances of carp hemoglobin, while present in the deoxy-type quaternary state of the carbonmonoxy and deoxy derivatives, is absent in the oxy-type quaternary state of both, in agreement with the assignments of these quaternary structures by other methods. The ring-current-shifted proton resonances (sensitive tertiary structural markers) of carp carbonmonoxyhemoglobin are substantially different from those of human normal adult hemoglobin. The aromatic proton resonance region of carp hemoglobin has fewer resonances than that of human normal adult hemoglobin, consistent with its much reduced histidine content. The hyperfine-shifted proximal histidyl NH-exchangeable proton resonances of carp hemoglobin suggest that during the transition from the oxy to the deoxy quaternary structure, there is a greater alteration in the heme pocket of one type of subunits (presumably the beta chain) than that in the other subunit. The present results suggest that there are differences in both tertiary and quaternary structures between carp and human normal adult hemoglobins which could contribute to the great differences in the functional properties between these two proteins.

Adult↗
PubMed1985

Lateral proton conduction at a lipid/water interface. Its modulation by physical parameters. Experimental and mathematical approaches.

Fast lateral proton conduction along the lipid/water interface has recently been experimentally demonstrated in our laboratory [Teissié, J., Prats, M., Soucaille, P. & Tocanne, J.F. (1985) Proc. Natl Acad. Sci. USA, in the press]. The present study gives a more precise description of the way various physical parameters can affect this process. The dependence of the distance covered by the proton on time is demonstrated to be quadratic. Increasing the speed of stirring in the injection compartment or the amount of injected acid or the contact between the monolayer and the acidic subphase increased the efficiency of the proton transfer. Raising the strength of the buffer in the bulk phase inhibited proton conduction. Results from experiments where the transfer of protons from the bulk phase to the interface was modified, suggested the occurrence of an 'energy barrier' limiting the access of protons from the bulk phase to the lipid polar head region.

Computers↗
PubMed1986

The proton channel, CF0, in thylakoid membranes. Only a low proportion of CF1-lacking CF0 is active with a high unit conductance (169 fS).

We investigated the conductance of pea thylakoid membranes and their capacity for photophosphorylation as function of the extraction of chloroplast coupling factor CF1. The degree of extraction was varied via the incubation time in EDTA-containing hypo-osmolar medium and was measured by rocket electroimmunodiffusion. The conductance of thylakoid membranes was measured by flash kinetic spectrophotometry. The time course of extraction followed the time course of thylakoid swelling. Contrary to expectation increasing loss of CF1 did not primarily increase the velocity of proton efflux from each vesicle. Instead proton-tight vesicles were converted to leaky ones, which lost phosphorylating activity. Two subpopulations occurred, although both types of vesicles, leaky and proton-tight ones, were CF1-depleted to a similar degree. This implied that only a small fraction of CF1-lacking CF0 was functional as a proton channel. Tight vesicles had no functional channels while leaky ones had at least one. We determined the proportion of tight vesicles in three independent ways: via the residual phosphorylation activity, via measurements of proton efflux and via measurements of the electric relaxation across the membrane. The results obtained were identical. A statistical evaluation of the data led us to the following conclusions. EDTA treatment produced vesicles containing approximately 10(5) chlorophyll molecules, equivalent to a total of approximately 100 CF0CF1 per vesicle. Even at the highest degree of extraction (75% of total CF1 extracted) only 2.5 out of 75 exposed CF0 per vesicle were proton-conducting. The unit conductance of one open CF0 channel was 169 +/- 18 fS at pH 7.5 and room temperature. At an electrical driving force of 100 mV this was equivalent to the passage of approximately 10(5) protons/s. The most important consequence of this relatively high unit conductance was that a single open CF0 channel was capable of dissipating the protonmotive force of one vesicle, thereby deactivating the whole remaining catalytic capacity of this vesicle.

Edetic Acid↗
PubMed1997

Fourier transform infrared spectroscopic studies of proton transfer processes and the dissociation of Zn2+-bound water in alcohol dehydrogenases.

The following complexes were investigated by Fourier transform difference spectroscopy: binary complexes of alcohol dehydrogenases from yeast (YADH) and horse liver (LADH) with nicotinamide adenine dinucleotide (NAD+) and adenosine (5')-diphospho(5)-beta-D-ribose (ADP-Rib); the binary complex of Zn2+-free YADH with NAD+, the ternary complex of LADH with NAD+ and 2,2,2-trifluoroethanol. After addition of NAD+ to YADH and LADH, protonation of the N1 atom of the adenine ring of NAD+ is observed. It is shown that this proton arises from the dissociation of the Zn2+-bound water. The interaction of the Zn2+ ion with water is very strong, since this interaction is not just an electrostatic interaction. If the Zn2+ ions are in a tetrahedral environment, a large covalent contribution also occurs. If ADP-Rib is present instead of NAD+, no protonation of the N1 atom of the adenine ring of ADP-Rib is found, which demonstrates that the positively charged nicotinamide ring favors the conduction of the positive charge. All these results confirm the mechanism of Brändén et al. (1975): the Zn2+-bound water is split and the arising (OH)- deprotonates the alcohol. In the case of the ternary complex of LADH with NAD+ and 2,2,2-trifluoroethanol, we demonstrate that the alcohol is deprotonated and the alcoholate ion is bound directly to the Zn2+ ion. The conduction of the proton from the active site to the N1 atom of adenine occurs via a hydrogen-bonded chain with large proton polarizability due to collective proton motion. The nature and mechanism of this pathway are discussed on the basis of data from previous studies.

Adenine↗
PubMed2004

Background potassium channel block and TRPV1 activation contribute to proton depolarization of sensory neurons from humans with neuropathic pain.

Protons cause a sustained depolarization of human dorsal root ganglion (DRG) neurons [Baumann et al. (1996) Pain, 65, 31-38]. In the present study we sought to determine which ion channels are expressed in human DRG neurons that could mediate the sustained responses observed in the patch-clamp recordings. RT-PCR of material from the DRG tissue revealed the presence of mRNAs for a nonselective cation channel that is activated by protons (TRPV1) and background potassium channels that are blocked by protons (TASK-1, TASK-3 and Kir2.3). Highly acidic solution (pH 5.4) applied to cultured DRG neurons evoked prolonged currents that were associated with a net increase in membrane conductance. Consistent with the involvement of TRPV1, these proton-evoked currents were blocked by capsazepine and were only found in neurons that responded to capsaicin with an increase in membrane conductance. Less acidic extracellular solution (pH 6.0) evoked such currents only rarely, but was able to strongly enhance the currents evoked by capsaicin. Capsazepine (1 microm) blocked the currents evoked by capsaicin at pH 7.35, as well as the potentiated responses to capsaicin at pH 6.0. In neurons that were not excited by capsaicin, moderate extracellular acidification (pH 6.0) caused a sustained decrease in resting membrane conductance. The decrease in membrane conductance by protons was associated with inhibition of background potassium channels. This excitatory effect of protons was not blocked by capsazepine. We conclude that in most neurons the sustained depolarization in response to moderately acidic solutions is the result of blocked background potassium channels. In a subset of neurons, TRPV1 also contributes.

Action Potentials↗
PubMed2004

Effect of proton pump inhibitors and antacid therapy on 13C urea breath tests and stool test for Helicobacter pylori infection.

OBJECTIVE: There is uncertainty about the best method of testing patients for Helicobacter pylori (H. pylori) infection while they are taking proton pump inhibitors. The aim of this study was to determine: (i) if the decreased sensitivity of the urea breath test during proton pump inhibitor is corrected by different techniques for breath testing and (ii) if the sensitivity of stool test is decreased with the administration of proton pump inhibitors. METHODS: Prospective randomized single-blind study was performed in a tertiary care university hospital. Out of 72 H. pylori infected patients endoscoped for upper abdominal symptoms 48 were randomized to proton pump inhibitors (omeprazole 20 mg each day or esomeprazole 40 mg each day) and 24 to antacid (aluminum hydroxide 800 mg each day) for 14 days. Several breath tests (standard 75 mg (13)C-UBT with citric acid, with orange juice, a tablet breath test with 100 and 50 mg of (13)C), and a stool test were carried out. Baseline samples were collected before and after treatment. RESULTS: The baseline sensitivity for all breath tests was 100% in both groups; for stool test it was 97.8% (95% CI: 88.7-96.6) and 90% (95% CI: 69.9-97.2) in the proton pump inhibitor and antacid group, respectively. After treatment, the sensitivity of tests was significantly low (UBTs range: 77.1%-85.4%; stool test: 83%; 95% CI: 63.9-91.1), while it was unchanged in the antacid group. CONCLUSIONS: False negative breath and stool tests are equally common in patients taking proton pump inhibitors. Antacids do not impair the sensitivity of the breath tests or the stool test.

Administration, Oral↗
PubMed2004

CYP2C19 polymorphism and proton pump inhibitors.

Proton pump inhibitors such as omeprazole (esomeprazole), lansoprazole, pantoprazole and rabeprazole are eliminated by the hepatic route and the polymorphic CYP2C19 is mainly involved in their metabolism. In different populations three phenotypes have been identified: extensive metabolizers, poor metabolizers and individuals carrying one wild type and one mutant allele (het extensive metabolizers). Systemic exposure to the proton pump inhibitors as expressed by the AUC (area under the plasma level time profiles) is 5-12-times higher in poor metabolizers than in extensive metabolizers. As the pharmacodynamic response (elevation of intragastric pH) to the proton pump inhibitors is related directly to their AUC, a much higher pH can be monitored over 24 hr in poor metabolizers than in extensive metabolizers. Furthermore, clinical efficacy of all proton pump inhibitors depend on maintaining intragastric pH above certain threshold levels and significantly higher eradication rates of Helicobacter pylori have been observed in patients of the poor metabolizers and het extensive metabolizers phenotype if compared to extensive metabolizers. Likewise, limited data suggest that proton pump inhibitors-induced healing rates in gastro-oesophageal reflux disease are apparently higher in poor metabolizers/het extensive metabolizers than in extensive metabolizers of CYP2C19. Therefore initial genotyping for this enzyme and higher dosage in extensive metabolizers is likely to improve the clinical efficacy of proton pump inhibitors.

Anti-Ulcer Agents↗
PubMedDate not supplied

A comparison of normal tissue complication probability of brain for proton and photon therapy of canine nasal tumors.

This study compared the calculated normal tissue complication probability of brain in dogs with a nasal tumor, which had both photon and proton treatment planning. Nine dogs diagnosed with a variety of histologies, but all with large, caudally located nasal tumors were studied. Three-dimensional (3-D) photon dose distribution, and a proton dose distribution was calculated for each dog. To calculate the normal tissue complication probability (NTCP) for brain, the partial brain volume irradiated with the prescribed dose was determined, then a mathematic model relating complications to partial volume and radiation dose was used. The NTCP was always smaller for proton plans as compared to photon plans, indicating conformation of the dose to the target allows a higher dose to be given. If a 5% NTCP were accepted, the mean applicable dose for this group of dogs was 50.2 Gy for photons, but 58.3 Gy for protons. Not all dogs would benefit the same from proton irradiation. If a large partial brain volume has to be irradiated, the advantage becomes minimal. There is also a minimal advantage if the planning target volume (PTV) includes a small, superficial brain volume. However, for a complex PTV shape the degree of conformation is clearly superior for protons and results in smaller calculated NTCPs.

Animals↗
PubMed2006

Consequences of long-term proton pump blockade: insights from studies of patients with gastrinomas.

Proton pump inhibitors are being increasingly used and for longer periods of time, especially in patients with gastroesophageal reflux disease. Each of these trends has led to numerous studies and reviews of the potential risk-benefit ratio of the long-term use of proton pump inhibitors. Both long-term effects of hypergastrinaemia due to the profound acid suppression caused by proton pump inhibitors as well as the effects of hypo-/achlorhydria per se have been raised and studied. Potential areas of concern that have been raised in the long-term use of proton pump inhibitors, which could alter this risk-benefit ratio include: gastric carcinoid formation; the development of rebound acid hypersecretion when proton pump inhibitor treatment is stopped; the development of tolerance; increased oxyntic gastritis in H. pylori patients and the possibility of increasing the risk of gastric cancer; the possible stimulation of growth of non-gastric tumours due to hypergastrinaemia; and the possible effect of the hypo/achlorhydria on nutrient absorption, particularly iron and vitamin B12. Because few patients with idiopathic gastro-oesophageal reflux disease/peptic ulcer disease have been treated long-term (i.e., >10 years), there is little known to address the above areas of potential concern. Most patients with gastrinomas with Zollinger-Ellison syndrome have life-long hypergastrinaemia, require continuous proton pump inhibitors treatment and a number of studies report results of >5-10 years of tratment and follow-up. Therefore, an analysis of Zollinger-Ellison syndrome patients can provide important insights into some of the safety concerns raised above. In this paper, results from studies of Zollinger-Ellison syndrome patients and other recent studies dealing with the safety concerns above, are briefly reviewed.

Animals↗
PubMed1981

Quantum chemical studies of proton transport through biomembranes.

A proposed mechanism of proton transport through biological membranes was investigated with the aid of ab initio molecular orbital methods. It requires the existence within a transmembrane protein of a hydrogen-bonded chain of residues. The full transport process was broken down into a number of simpler steps, each of which involves the transfer of a proton from one residue to the next along the chain. The hydroxyl-containing residues were modeled by water molecules. Linear hydrogen-bonded systems H+ (H2O)n, n = 2, 3, 4, 5 were studied using the 4-31G basis set. The dimer was shown to furnish an excellent model for study of proton transfer in larger systems. Deformations of the hydrogen bond lead to large increases in the energy barrier to proton transfer. Certain properties of the electron density distribution show a close correspondence with transfer energetics; consequently, they may have some predictive use. The transition state to double proton transfer in the trimer and pentamer involve partial transfer of only one proton. Implications of the above observations upon the proposed mechanism were discussed.

Biological Transport↗
PubMed1992

Transformation of a bop-hop-sop-I-sop-II-Halobacterium halobium mutant to bop+: effects of bacteriorhodopsin photoactivation on cellular proton fluxes and swimming behavior.

We have transformed Pho81, a Halobacterium halobium mutant strain which does not contain any of the four retinylidene proteins known in this species, with the bop gene cluster to create Pho81BR, a BR+HR-SR-I-SR-II-strain. The absorption spectrum, pigment reconstitution process, light-dark adaptation and photochemical reaction cycle of the expressed protein are indistinguishable from those of native bacteriorhodopsin (BR) in purple membrane of wild type strains. Strain Pho81BR permits for the first time characterization of effects of BR photoactivation alone on cell swimming behavior and energetics in the absence of the spectrally similar phototaxis receptor sensory rhodopsin I (SR-I) and electrogenic chloride pump halorhodopsin (HR). A non-adaptive upward shift in spontaneous swimming reversal frequency occurs following 3 s of continuous illumination of Pho81BR cells with green light (550 +/- 20 nm). This effect is abolished by low concentrations of the proton ionophore carbonylcyanide m-chlorophenylhydrazone. Although BR does not mediate phototaxis responses in energized Pho81BR cells under our culture conditions, proton pumping by BR in Pho81BR cells partially deenergized by inhibitors of respiration and adenosine triphosphate synthesis results in a small attractant response. Based on our measurements, we attribute the observed effects of BR photoactivation on swimming behavior to secondary consequences of electrogenic proton pumping on metabolic or signal transduction pathways, rather than to primary sensory signaling such as that mediated by SR-I. Proton extrusion by BR activates gated proton influx ports resulting in net proton uptake in wild-type cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriorhodopsins↗
PubMed1987

Proton-induced transformation of calcium channel in chick dorsal root ganglion cells.

1. In dissociated and cultured 2-5-day-old chick dorsal root ganglion cells, a large transient inward current could be activated in response to a 'step' increase in [H+]o. 2. Using the single-electrode patch clamp technique in its whole-cell configuration, the proton-induced current was graded with [H+]o and relaxed in 1-2 s. 3. The pH dependence of the current was sigmoid with activation occurring at around pH 7.0 (at[Ca2+]o = 1 mM) and a maximum at pH 6.0-5.5. 4. Small increases of [H+]o, which by themselves failed to activate a significant amount of current, inactivated the proton-induced current. The half-maximum of inactivation occurred at pH 7.11 at [Ca2+]o = 5 mM, but this changed to pH 7.32 at [Ca2+]o = 1 mM. 5. The proton-induced inward current reversed direction at the Na+ equilibrium potential and was suppressed in the absence of [Na+]o. Measurement of the reversal potential at different [Na+]o and/or [Na+]i showed a linear relation with a slope of 58 mV/decade as predicted from the Nernst equation. Thus, proton-induced current was carried by Na+ and was abbreviated as INa(H). 6. The membrane conductance associated with INa(H) showed no voltage dependence, but did change in parallel with the activation of the current. The membrane conductance increased by a factor of 10-20-fold at the peak of the inward current. 7. INa(H) was blocked by organic and inorganic Ca2+ channel blockers (diltiazem, Cd2+ and Ni2+), but was unaffected by high concentrations of tetrodotoxin (TTX) or steady-state increases of the [Ca2+]i to 10(-4) M or the [H+]i to 10(-6) M. 8. In outside-out membrane patches, the single channel associated with the proton-induced current opened in bursts, with long pauses. The mean open time during the bursts was 1.26 ms and the channel had a conductance of 20-25 pS at -80 mV (120 mM [Na2+]o, 20 mM [Na2+]i). 9. Measurement of the voltage-gated Ca2+ current using short (30-50 ms) depolarizing pulses to zero showed that the Ca2+ current (ICa) but not the fast Na+ current (INa) was completely suppressed during the time course of activation of INa(H). 10. INa(H) was completely blocked by high (35-40 mM) [Ca2+]o. 11. Simultaneous elevation of [H+]o and [Ca2+]o failed to activate INa(H) but enhanced the voltage-gated Ca2+ channel. 12. Our data show that the proton-induced current is carried by Na+ flowing through a transformed Ca2+ channel.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed2002

A correction method for diamond detector signal dependence with proton energy.

Small dosimeters as solid state detectors can be useful for the dosimetric characterization and periodic quality control of radiotherapy proton beams. The calibration of solid state detectors for proton beams is not a solved problem especially for ophthalmologic proton beams, where these detectors present a LET-dependent signal. In this work a PTW diamond detector has been selected because of its good signal reproducibility (0.3%) and stable response with accumulated dose. A method that takes into account the LET dependence of the diamond detector signal, at 62 MeV proton beam, is here proposed. In particular an empirical correction factor, kDD(Eo) (Rres), has been determined as a function of the residual range quality index, to correct the diamond detector signal for a proton beam of incident effective energy E0= 62 MeV. A dedicated software allows us to use the diamond detector as an on-line reference dosimeter, where an ionization chamber may be difficult to use, or for periodic quality control procedures. The article also reports a comparison between the signal dependence on proton energy of silicon, diamond, and radiochromic film detectors.

Biophysical Phenomena↗