Insensitive Component Research Articles

Entangled Entrepreneurial Competitiveness Advantage: An Opinion Paper

The economic action of any individual seems to be guided by psychological components belonging, often more to the sphere of the intuitive rather than to the logical mind. Cognitive Economics, unlike other critical approaches to neoclassical rationality, is aware of this reality and moves the center of gravity of the theory of the mind of the economic actor from the aspects of conscious, explicit, intentional, and rational towards the tacit, sub-conscious, intuitive and emotional. Cognitive Economics, as empirical theory, par excellence, does not refuse to consider the contribution of the mind to an economic decision. The role of the psyche in many situations of choice is undeniable. It is not, however, the only cognitive reality responsible for economic choices. From this point of view, the concept of limited rationality, remaining within a vision of intentionality in cognitive activities, loses much of its explanatory capacity. One of the motives for economic action is limited rationality because there is not enough computational capacity for calculating the consciousness and the intentions of the human mind. Rationality is also limited through the influence of intuitive, affective, emotional, and silent factors, which all characterize what we have called the intuitive mind. The economic actor’s mind theory is based on cognitive duplicity, integrating the insensitive and the intuitive component depending on the situations and contexts of a decision. However, there are few situations in which we can say that the insensitive component takes the decision without influence of that intuitive. A small part of the mind emerges to the surface image of the economic actor, which characterizes some of the intuitive. But it rests on the larger submerged body of the mind, which is not visible but responsible for guiding the inferential paths of homo-economicus. The’ cognitive economy assumes that this duality of the human mind and the primacy of the intuitive component explains economic action.

Securitization and Liquidity Creation in Markets with Adverse Selection

This paper provides an information-based theory of tranching, a practice in which sellers slice a financial asset into debt securities with different seniority. I use the price posting framework to analyze asset-backed security markets with adverse selection and find that tranching is a robust equilibrium outcome. Tranching decomposes the asset into “information insensitive” and “information sensitive” components. The expected cash flow of the information insensitive component is independent of the seller's private signal, whereas the expected cash flow of the information sensitive component varies with the signal. When buyers are restricted to trade shares of assets, they have to purchase both components proportionally. Tranching, however, allows buyers to disproportionately purchase the information insensitive component. As a result, buyers are less concerned about adverse selection, and total trading volume in the market increases. My model also generates testable predictions on the liquidity of individual debt securities: the selling probability of a debt security increases in its seniority, which is observable to buyers, yet decreases with its performance, which is ex-ante unobservable to buyers; these predictions are supported by my empirical analysis of the non-agency MBS market.

Restoration of uridine 5′-triphosphate-suppressed delayed rectifying K+ currents by an NO activator KMUP-1 involves RhoA/Rho kinase signaling in pulmonary artery smooth muscle cells

We have demonstrated that KMUP-1 (7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) blunts monocrotaline-induced pulmonary arterial hypertension by altering Ca2+ sensitivity, K+-channel function, endothelial nitric oxide synthase activity, and RhoA/Rho kinase (ROCK) expression. This study further investigated whether KMUP-1 impedes uridine 5′-triphosphate (UTP)-inhibited delayed rectifying K+ (KDR) current in rat pulmonary arteries involved the RhoA/ROCK signaling. Pulmonary artery smooth muscle cells (PASMCs) were enzymatically dissociated from rat pulmonary arteries. KMUP-1 (30μM) attenuated UTP (30μM)-mediated membrane depolarization and abolished UTP-enhanced cytosolic Ca2+ concentration. Whole-cell patch-clamp electrophysiology was used to monitor KDR currents. A voltage-dependent KDR current was isolated and shown to consist of a 4-aminopyridine (5mM)-sensitive component and an insensitive component. The 4-aminopyridine sensitive KDR current was suppressed by UTP (30μM). The ROCK inhibitor Y27632 (30μM) abolished the ability of UTP to inhibit the KDR current. Like Y27632, KMUP-1 (30μM) similarly abolished UTP-inhibited KDR currents. Superfused protein kinase A and protein kinase G inhibitors (KT5720, 300nM and KT5823, 300nM) did not affect UTP-inhibited KDR currents, but the currents were restored by adding KMUP-1 (30μM) to the superfusate. KMUP-1 reversal of KDR current inhibition by UTP predominantly involves the ROCK inhibition. The results indicate that the RhoA/ROCK signaling pathway plays a key role in eliciting PASMCs depolarization caused by UTP, which would result in pulmonary artery constriction. KMUP-1 blocks UTP-mediated PASMCs depolarization, suggesting that it would prevent abnormal pulmonary vasoconstriction.

Partially dissecting the steady-state electron fluxes in Photosystem I in wild-type and pgr5 and ndh mutants of Arabidopsis.

Cyclic electron flux (CEF) around Photosystem I (PS I) is difficult to quantify. We obtained the linear electron flux (LEFO2) through both photosystems and the total electron flux through PS I (ETR1) in Arabidopsis in CO2-enriched air. ΔFlux = ETR1 – LEFO2 is an upper estimate of CEF, which consists of two components, an antimycin A-sensitive, PGR5 (proton gradient regulation 5 protein)-dependent component and an insensitive component facilitated by a chloroplastic nicotinamide adenine dinucleotide dehydrogenase-like complex (NDH). Using wild type as well as pgr5 and ndh mutants, we observed that (1) 40% of the absorbed light was partitioned to PS I; (2) at high irradiance a substantial antimycin A-sensitive CEF occurred in the wild type and the ndh mutant; (3) at low irradiance a sizable antimycin A-sensitive CEF occurred in the wild type but not in the ndh mutant, suggesting an enhancing effect of NDH in low light; and (4) in the pgr5 mutant, and the wild type and ndh mutant treated with antimycin A, a residual ΔFlux existed at high irradiance, attributable to charge recombination and/or pseudo-cyclic electron flow. Therefore, in low-light-acclimated plants exposed to high light, ΔFlux has contributions from various paths of electron flow through PS I.

Renal HCO3‐ Reabsorption Is Differentially Modulated by Water Deprivation Depending on Food / Na+ Intake

Although kidneys are able to perform water balance dissociated from Na+ balance, hypovolemic dehydration, as seen during water deprivation (WD), modifies both. Moreover, WD can occur singly or together with food deprivation (FD) and, therefore, may differently alter such parameters. NHE3 is the major pathway for NaHCO3‐ in the proximal tubule and is important to volume balance, but the effect of WD on it is not well known. The goal of this work was to determine the effect of WD on HCO3‐ reabsorption (JHCO3‐) and the role of food (FI) or Na (NaI) intake in this mechanism. Rats were kept for 24 hs with water ad libitum (CTRL) or in WD, and JHCO3‐ was measured by means of stationary microperfusion. WD decreased by 34% JHCO3‐ (vs CTRL), and this effect was NHE3‐dependent, since the S3226(NHE3‐inhibitor)‐insensitive component of JHCO3‐ was not modulated by WD. Because NaI increases renal Na+ excretion and could influence JHCO3‐, animals were kept in WD and fed with a deficient Na+ diet (DNa), to determine the role of NaI on WD effect. As expected, in the absence of dietary Na+, JHCO3‐ was stimulated. Moreover, despite during WD + DNa, JHCO3‐ has decreased by 13% (vs DNa alone), the inhibitory effect of WD on JHCO3‐ was attenuated (since WD decreased JHCO3‐ by 34% when animals were fed with a CTRL diet). Because others dietary components besides Na+, may influence JHCO3‐, animals were kept in FD and WD. Although NaI was null during both, DNa and FD, JHCO3‐ was not stimulated by this last condition. Besides, the observed attenuation on JHCO3‐ was smaller (JHCO3‐ was 13% for DNa vs DNa + WD and 26% for FD vs FD + WD). These results indicate that WD inhibits NHE3. NaI presents a central role in this inhibitory effect; however NI has also a Na+‐independent component that inhibits JHCO3‐.Financial support FAPESP, CNPq

In vitro relaxant and spasmolytic effects of essential oil of Pistacia integerrima Stewart ex Brandis Galls

Ethnopharmacological relevancePistacia integerrima J.L. Stewart ex Brandis (Family: Anacardiaceae) galls are used in Indian ethnomedicine for its anti-asthmatic, sedative and spasmolytic properties, however, there are no scientific studies demonstrating its spasmolytic activity. The present investigation deals with the evaluation of relaxant and spasmolytic activities of the essential oil isolated from the galls of Pistacia integerrima J.L. Stewart ex Brandis (EOPI). Materials and methodsIn vitro pharmacological assays were carried out on rabbit jejunum spontaneous contractions, guinea pig ileum. The present investigation studied the relaxation of basal tone of isolated guinea pig ileum by possible involvement of NO, prostaglandins, membrane Na+ channels, potassium channel, enteric nervous system, adrenoceptors, Ca2+ channels. Additional studies were conducted for comparison of the relaxant effects of EOPI on CaCl2 induced contraction in calcium free tyrode solution, effect on nifedipine insensitive component of ACh-induced contraction and on the contractile machinery to intracellular [Ca2+] on isolated guinea pig ileum. ResultsEOPI at non-relaxing dose potentiated the isoprenaline induced relaxation of rabbit jejunum. EOPI (50µg/mL) exhibited 28% relaxation of basal tone of 60mMK+ induced contraction which is unaltered by preincubation with 0.5mM hexamethonium, 0.5µM Tetrodotoxin, 1µM indomethacin, and 100µML-NG-Nitroarginine Methyl Ester (L-NAME). EOPI inhibited Ca2+ induced contraction of isolated guinea pig ileum in Ca2+ free medium. EOPI (10µg/ml) potentiated the reversal of a KCl-induced tonic contraction has been observed in Ca2+ free medium. ConclusionThe present investigation reinforces the use of Pistacia integerrima Stewart ex Brandis as antispasmodic in folk medicine. Moreover, it is demonstrated the involvement of β- adrenoceptors and calcium channels in this activity, but not the participation of nicotinic receptors, Na+ channels, prostaglandins or nitric oxide.

Nitric oxide suppresses vascular voltage-gated T-type Ca2+ channels through cGMP/PKG signaling

Recent reports have noted that T-type Ca2+ channels (CaV3.x) are expressed in vascular smooth muscle and are potential targets of regulation. In this study, we examined whether and by what mechanism nitric oxide (NO), a key vasodilator, influences this conductance. Using patch-clamp electrophysiology and rat cerebral arterial smooth muscle cells, we monitored an inward Ba2+ current that was divisible into a nifedipine-sensitive and -insensitive component. The latter was abolished by T-type channel blocker and displayed classic T-type properties including faster activation and steady-state inactivation at hyperpolarized potentials. NO donors (sodium nitroprusside, S-nitroso-N-acetyl-dl-penicillamine), along with activators of protein kinase G (PKG) signaling, suppressed T-type currents. Inhibitors of guanylyl cyclase/PKG {1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and KT5823, respectively}, had no effect on basal currents; KT5823 did, however, mask T-type Ca2+ channel current inhibition by NO/PKG. Functional experiments confirmed an inhibitory effect for NO on the T-type contribution to cerebral arterial myogenic tone. Cumulatively, our findings support the view that T-type Ca2+ channels are a regulatory target of vasodilatory signaling pathways. This targeting will influence Ca2+ dynamics and consequent tone development in the cerebral circulation.

Effects of ammonium nitrate, cesium chloride and tetraethylammonium on high-affinity potassium uptake in habanero pepper plantlets (Capsicum chinense Jacq.)

Potassium (K + ) is an essential nutrient and the most abundant cation in plant cells. Plants have a wide variety of transport systems for K + acquisition that catalyze K + uptake across a wide spectrum of external K + concentrations and mediate K + movement within the plant, as well as its release into the environment. The KUP/HAK/KT transporter family plays a key role in K + homeostasis in plant cells. The present study demonstrates that habanero pepper plantlets have a clear pattern of K + uptake when resupplemented with K + after K + starvation. Habanero pepper plantlets, re-supplemented with a solution containing low concentrations of K + after 72, 96 or 120 h of K + starvation were able to decrease the amount of K + in the solution at different time points. To study the effect of NH 4 + , we added different concentrations of NH 4 NO 3 to the medium solution and demonstrated that NH 4 + inhibited K + uptake in a dose-dependent manner. When the plantlets were subjected to K + starvation for 72 h and then resupplemented with 50 or 100 μM K + , exposure to K + channel blockers (10 mM CsCl and 20 mM TEA) decreased their K + uptake compared with the control treatment. A model demonstrating the process of K + uptake through an NH 4 + -insensitive component was proposed. Key words : Potassium, high affinity transporters, channel blockers, ammonium.

Molecular mapping of the AOX1a and β-AmyI genes in potato

With 1 figure and 1 table Abstract Two genes, AOX1a and β-AmyI, were mapped in diploid potato. AOX1a (alternative oxidase 1a) is the cyanide insensitive component of the electron transport chain in plants induced by environmental stress. The enzyme β-amylase (β-AmyI) is involved in hydrolytic starch breakdown in both photosynthetic and storage organs. AOX1a and β-AmyI are located in the central region on potato chromosome VIII, where other genes for potato tuber quality traits were mapped.

In vitro activation of the medial septum—Diagonal band complex generates atropine‐sensitive and atropine‐resistant hippocampal theta rhythm: An investigation using a complete septohippocampal preparation

The medial septum and diagonal band complex (MS-DB) is believed to play a key role in generating theta oscillations in the hippocampus, a phenomenon critical for learning and memory. Although the importance of the MS-DB in hippocampal theta rhythm generation is generally accepted, it remains to be determined whether the MS-DB alone can generate hippocampal oscillations or is only a transducer of rhythmic activity from other brain areas. Secondly, it is known that hippocampal theta rhythm can be separated into an atropine-sensitive and insensitive component. However, it remains to be established if the MS-DB can generate both types of rhythm. To answer these questions, we used a new in vitro rat septohippocampal preparation placed in a hermetically separated two side recording chamber. We showed that carbachol activation of the MS-DB generated large theta oscillations in the CA1 and CA3 regions of the hippocampus. These oscillations were blocked by applying either the GABA(A) receptor antagonist bicuculline or the AMPA/kainate antagonist DNQX to the hippocampus. Interestingly, the application of the muscarinic receptor antagonist atropine produced only a partial decrease in the amplitude, without modification of the frequency, of theta. These results show for the first time, that upon optimal excitation, the MS-DB alone is able to generate hippocampal oscillations in the theta frequency band. Moreover, these MS-DB generated theta oscillations are mediated by muscarinic and nonmuscarinic receptors and have a pharmacological profile similar to theta rhythm observed in awake animals.

A mechanism distinct from the L-type Ca current or Na–Ca exchange contributes to Ca entry in rat ventricular myocytes

The aim of this paper was to characterize the pathways that allow Ca 2+ ions to enter the cell at rest. Under control conditions depolarization produced an increase of intracellular Ca concentration ([Ca 2+] i) that increased with depolarization up to about 0 mV and then declined. During prolonged depolarization the increase of [Ca 2+] i decayed. This increase of [Ca 2+] i was inhibited by nifedipine and the calculated rate of entry of Ca increased on depolarization and then declined with a similar timecourse to the inactivation of the L-type Ca current. We conclude that this component of change of [Ca 2+] i is due to the L-type Ca current. If intracellular Na was elevated then only part of the change of [Ca 2+] i was inhibited by nifedipine. The nifedipine- insensitive component increased monotonically with depolarization and showed no relaxation on prolonged depolarization. This component appears to result from Na–Ca exchange (NCX). When the L-type current and NCX were both inhibited (nifedipine and Na-free solution) then depolarization decreased and hyperpolarization increased [Ca 2+] i. These changes of [Ca 2+] i were unaffected by modifiers of B-type Ca channels such as chlorpromazine and AlF 3 but were abolished by gadolinium ions. We conclude that, in addition to L-type Ca channels and NCX, there is another pathway for entry of Ca 2+ into the ventricular myocyte but this is distinct from the previously reported B-type channel.

Optical studies of nicotinic acetylcholine receptor subtypes in the guinea-pig enteric nervous system

Nicotinic transmission in the enteric nervous system (ENS) is extensive, but the role of individual nicotinic acetylcholine receptor (nAChR) subtypes in the functional connectivity of its plexuses has been elusive. Using monoclonal antibodies (mAbs) against neuronal alpha3-, alpha4-, alpha3/alpha5-, beta2-, beta4- and alpha7-subunits, combined with radioimmunoassays and immunocytochemistry, we demonstrate that guinea-pig enteric ganglia contain all of these nAChR-subunits with the exception of alpha4, and so, differ from mammalian brain. This information alone, however, is insufficient to establish the functional role of the identified nAChR-subtypes within the enteric networks and, ultimately, their specific contributions to gastrointestinal physiology. We have used voltage-sensitive dyes and a high-speed CCD camera, in conjunction with specific antagonists to various nAChRs, to elucidate some of the distinct contributions of the individual subtypes to the behaviour of enteric networks. In the guinea-pig, the submucous plexus has the extraordinary advantage that it is virtually two-dimensional, permitting optical recording, with single cell resolution, of the electrical activity of all of its neurones. In this plexus, the block of alpha3beta2-, alpha3beta4- and/or alpha7-nAChRs always results in a decrease in the magnitude of the synaptic response. However, the magnitude of the fast excitatory post-synaptic potentials (epsps) evoked by electrical stimulation of a neighbouring ganglion varies from cell to cell, reflecting the differential expression of subunits already observed using mAbs, as well as the strengths of the activated synaptic inputs. At the same time, we observe that submucous neurones have a substantial mecamylamine (Mec)-insensitive (non-nicotinic) component to their fast epsps, which may point to the presence of purinergic or serotonergic fast epsps in this system. In the myenteric plexus, on the other hand, the antagonist-induced changes in the evoked synaptic response vary depending upon the location of the stimulating electrode with respect to the ganglion under study. The range of activity patterns that follows sequential pharmacological elimination of individual subtypes suggests that nAChRs may be capable of regulating the activity of both excitatory and inhibitory pathways, in a manner similar to that described in the central nervous system.

Concurrent Stimulation of Cannabinoid CB1 and Dopamine D2 Receptors Enhances Heterodimer Formation: A Mechanism for Receptor Cross-Talk?

Dopamine and endogenous cannabinoids display complex interactions in the basal ganglia. One possible level of interaction is between CB1 cannabinoid and D2 dopamine receptors. Here, we demonstrate that a regulated association of CB1 and D2 receptors profoundly alters CB1 signaling. This provides the first evidence that CB1/D2 receptor complexes exist, are dynamic, and are agonist-regulated with highest complex levels detected when both receptors are stimulated with subsaturating concentrations of agonist. The consequence of this interaction is a differential preference for signaling through a "nonpreferred" G protein. In this case, D2 receptor activation, simultaneously with CB1 receptor stimulation, results in the receptor complex coupling to G alpha s protein in preference to the expected G alpha i/o proteins. The result of this interaction is an increase in the second messenger cAMP, reversing an initial synergistic inhibition of adenylyl cyclase activity seen at subthreshold concentrations of cannabinoid agonist. Additionally, a pertussis toxin insensitive component in the activation of extracellular signal-regulated kinase (ERK) 1/2 kinases by the cannabinoid agonist CP 55,940 [(1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol] is revealed in cells stably expressing both CB1 and D2 receptors. Thus, concurrent receptor stimulation promotes a heterooligomeric receptor complex and an apparent shift of CB1 signaling from a pertussis toxin-sensitive inhibition to a partly pertussis toxin-insensitive stimulation of adenylyl cyclase and ERK 1/2 phosphorylation.

C75 activates malonyl-CoA sensitive and insensitive components of the CPT system

Carnitine palmitoyltransferase I (CPT-I) and II (CPT-II) enzymes are components of the carnitine palmitoyltransferase shuttle system which allows entry of long-chain fatty acids into the mitochondrial matrix for subsequent oxidation. This system is tightly regulated by malonyl-CoA levels since this metabolite is a strong reversible inhibitor of the CPT-I enzyme. There are two distinct CPT-I isotypes (CPT-Iα and CPT-Iβ), that exhibit different sensitivity to malonyl-CoA inhibition. Because of its ability to inhibit fatty acid synthase, C75 is able to increase malonyl-CoA intracellular levels. Paradoxically it also activates long-chain fatty acid oxidation. To identify the exact target of C75 within the CPT system, we expressed individually the different components of the system in the yeast Pichia pastoris. We show here that C75 acts on recombinant CPT-Iα, but also on the other CPT-I isotype (CPT-Iβ) and the malonyl-CoA insensitive component of the CPT system, CPT-II.

Regulation of K+ transport in tomato roots by the TSS1 locus. Implications in salt tolerance.

The tss1 tomato (Lycopersicon esculentum) mutant exhibited reduced growth in low K+ and hypersensitivity to Na+ and Li+. Increased Ca2+ in the culture medium suppressed the Na+ hypersensitivity and the growth defect on low K+ medium of tss1 seedlings. Interestingly, removing NH4+ from the growth medium suppressed all growth defects of tss1, suggesting a defective NH4(+)-insensitive component of K+ transport. We performed electrophysiological studies to understand the contribution of the NH4(+)-sensitive and -insensitive components of K+ transport in wild-type and tss1 roots. Although at 1 mm Ca2+ we found no differences in affinity for K+ uptake between wild type and tss1 in the absence of NH4+, the maximum depolarization value was about one-half in tss1, suggesting that a set of K+ transporters is inactive in the mutant. However, these transporters became active by raising the external Ca2+ concentration. In the presence of NH4+, a reduced affinity for K+ was observed in both types of seedlings, but tss1 at 1 mm Ca2+ exhibited a 2-fold higher Km than wild type did. This defect was again corrected by raising the external concentration of Ca2+. Therefore, membrane potential measurements in root cells indicated that tss1 is affected in both NH4(+)-sensitive and -insensitive components of K+ transport at low Ca2+ concentrations and that this defective transport is rescued by increasing the concentration of Ca2+. Our results suggest that the TSS1 gene product is part of a crucial pathway mediating the beneficial effects of Ca2+ involved in K+ nutrition and salt tolerance.

Pyrimidine nucleotides suppress KDRcurrents and depolarize rat cerebral arteries by activating Rho kinase

This study examined whether, and by what signaling and ionic mechanisms, pyrimidine nucleotides constrict rat cerebral arteries. Cannulated cerebral arteries stripped of endothelium and pressurized to 15 mmHg constricted in a dose-dependent manner to UTP. This constriction was partly dependent on the depolarization of smooth muscle cells and the activation of voltage-operated Ca(2+) channels. The depolarization and constriction induced by UTP were unaffected by bisindolylmaleimide I, a PKC inhibitor that abolished phorbol ester (PMA)-induced constriction in cerebral arteries. In contrast, the Rhokinase inhibitor Y-27632 attenuated the ability of UTP to both constrict and depolarize cerebral arteries. With patch-clamp electrophysiology, a voltage-dependent delayed rectifying K(+) (K(DR)) current was isolated and shown to consist of a slowly inactivating 4-aminopyridine (4-AP)-sensitive and an -insensitive component. The 4-AP-sensitive K(DR) current was potently suppressed by UTP through a mechanism that was not dependent on PKC. This reflects observations that demonstrated that 1) a PKC activator (PMA) had no effect on K(DR) and 2) PKC inhibitors (calphostin C or bisindolylmaleimide I) could not prevent the suppression of K(DR) by UTP. The Rho kinase inhibitor Y-27632 abolished the ability of UTP to inhibit the K(DR) current, as did inhibition of RhoA with C3 exoenzyme. Cumulatively, these observations indicate that Rho kinase signaling plays an important role in eliciting the cerebral constriction induced by pyrimidine nucleotides. Moreover, they demonstrate for the first time that Rhokinase partly mediates this constriction by altering ion channels that control membrane potential and Ca(2+) influx through voltage-operated Ca(2+) channels.

Anion-dependent Mg2+ influx and a role for a vacuolar H+-ATPase in sheep ruminal epithelial cells.

The K+-insensitive component of Mg2+ influx in primary culture of ruminal epithelial cells (REC) was examined by means of fluorescence techniques. The effects of extracellular anions, ruminal fermentation products, and transport inhibitors on the intracellular free Mg2+ concentration ([Mg2+]i), Mg2+ uptake, and intracellular pH were determined. Under control conditions (HEPES-buffered high-NaCl medium), the [Mg2+]i of REC increased from 0.56 +/- 0.14 to 0.76 +/- 0.06 mM, corresponding to a Mg2+ uptake rate of 15 microM/min. Exposure to butyrate did not affect Mg2+ uptake, but it was stimulated (by 84 +/- 19%) in the presence of CO2/HCO(-)3. In contrast, Mg2+ uptake was strongly diminished if REC were suspended in HCO(-)3-buffered high-KCl medium (22.3 +/- 4 microM/min) rather than in HEPES-buffered KCl medium (37.5 +/- 6 microM/min). After switching from high- to low-Cl- solution, [Mg2+]i was reduced from 0.64 +/- 0.09 to 0.32 +/- 0.16 mM and the CO2/HCO(-)3-stimulated Mg2+ uptake was completely inhibited. Bumetanide and furosemide blocked the rate of Mg2+ uptake by 64 and 40%, respectively. Specific blockers of vacuolar H+-ATPase reduced the [Mg2+]i (36%) and Mg2+ influx (38%) into REC. We interpret this data to mean that the K+-insensitive Mg2+ influx into REC is mediated by a cotransport of Mg2+ and Cl- and is energized by an H+-ATPase. The stimulation of Mg2+ transport by ruminal fermentation products may result from a modulation of the H+-ATPase activity.

The heterogeneity of central benzodiazepine receptor subtypes in the human hippocampal formation, frontal cortex and cerebellum using [ 3H]flumazenil and zolpidem

The ability of clonazepam and zolpidem to displace [ 3H]flumazenil binding was measured in the human hippocampal formation, frontal cortex (BA9) and the cerebellum using in situ radioligand binding and autoradiography. The use of high resolution phosphorimaging in all regions indicated the displacement of [ 3H]flumazenil by clonazepam was monophasic with K i values ranging from 2.73±0.17 to 6.49±0.21 nM. [ 3H]flumazenil binding that was not displaced by clonazepam ranged from 3.39±0.86 to 7.15±1.11%. The ability of zolpidem to displace [ 3H]flumazenil was also monophasic in the frontal cortex and cerebellum with K i values of 37.53±1.79 and 31.80±1.68 nM, respectively. In contrast, within all hippocampal regions, zolpidem displacement of [ 3H]flumazenil was biphasic, with K i values for the high affinity site ranging from 0.13±0.04 to 0.54±0.03 nM, whereas the low affinity site was between 84.98±1.58 and 98.84±1.89 nM. In addition, zolpidem insensitive [ 3H]flumazenil binding was observed to vary markedly between brain regions, ranging between 37.85±1.60 and 6.13±0.83%. In conclusion, the present results indicate that in situ radioligand binding and high-resolution phosphorimaging techniques can be utilized to measure the differential displacement of [ 3H]flumazenil by zolpidem and clonazepam. Moreover, our data suggests that the differential distribution of the zolpidem insensitive component of [ 3H]flumazenil binding is an indicator of GABA/BZ receptors assembled by different subunits within the human brain.

Nicotine-evoked transmitter release from synaptosomes: functional association of specific presynaptic acetylcholine receptors and voltage-gated calcium channels.

It has previously been shown that nicotine-evoked dopamine release from rat striatal synaptosomes and nicotine-evoked norepinephrine release from hippocampal synaptosomes are mediated by distinct nicotinic acetylcholine receptor (nAChR) subtypes. In the present study, the functional association of these nicotinic receptors with specific subtypes of voltage-gated calcium channels was examined. Cd(2+) (200 microM), as well as omega-conotoxin MVIIC (5 microM), blocks approximately 85% of nicotine-evoked dopamine release from striatal synaptosomes, indicating a major involvement of calcium channels. Furthermore, the toxin-susceptibility suggests that these calcium channels contain alpha(1A) and/or alpha(1B) subunits. Inhibition of nicotine-evoked dopamine release by conotoxins alpha-MII and omega-GVIA is additive and indicates that presynaptic alpha3beta2 nAChRs are functionally coupled to alpha(1A), but not alpha(1B), calcium channel subtypes. Conversely, insensitivity to alpha-AuIB and sensitivity to omega-MVIIC indicate that non-alpha3beta2/alpha3beta4-containing nAChRs are functionally coupled to alpha(1B)-containing calcium channels. In contrast, Cd(2+) blocks only 65% of nicotine-evoked norepinephrine release from hippocampal synaptosomes, indicating that a substantial fraction of this release occurs through mechanisms not involving calcium channels. This Cd(2+)-insensitive component of release is blocked by alpha-AuIB and therefore appears to be triggered by Ca(2+) flowing directly through the channels of presynaptic alpha3beta4 nAChRs. Thus, these data indicate that different presynaptic termini can have distinctive functional associations of specific nAChRs and voltage-gated calcium channels.

Ray transfer matrices for one kind of constant deviation prism: Short Note

Abstract One kind of constant deviation prisms which can invariably transform the propagating direction of a ray or a beam is analyzed in this paper. Its transfer characteristics could be described by 2×2 matrix and its misaligned transfer characteristics could be described by 3×3 augmented matrix. Under the condition of manufacturing tolerance, its transfer matrices are also given. And it is shown that the constant deviation prism is a two-dimensional insensitive component.