Spectroscopic properties and temperature induced electronic configuration changes of all-<Emphasis Type="Italic">trans</Emphasis> and 15-<Emphasis Type="Italic">cis</Emphasis> β-carotenes in ionic liquids

The clear vibrational structure of fluorescence spectrum of β-carotene in the solvent is reported for the first time at room temperature. This finding is in good agreement with recently discovered covalent 3 ¹A _g ⁻ new carotenoid state. The fluorescence yield of β-carotene in ionic liquid (1-methyl-3-octyloxymethylimidazolium tetrafluoroborate) is around hundred times higher than in standard solvent n-hexane. The all-trans and 15-cis β-carotene fluorescence yields in ionic liquid are 1.96±0.03 and 2.53±0.03 %, respectively. The ionic liquid is a very useful tool for modelling photosynthetic system in situ. We present the electronic absorption data of β-carotene in ionic liquids (so called neoteric solvents) with special interest in the absorption changes as a function of temperature in the range 0–90 °C (273–363 K). Ionic liquids are also very good medium for temperature study, because they are not changing up to several hundred °C and also not evaporating during heating. The relationship between spectral characteristics of β-carotene in new generation solvents with increasing and decreasing temperature is evaluated. The energy value of the ionic state 1 ¹B _u ⁺ of synthetic β-carotene in ionic liquids exhibits a linear and temperature reversible dependence on temperature up to 30 °C (303 K) and up to 40 °C (313 K) for 15-cis and all-trans β-carotenes, respectively. This is valid for both 0-0 and 0-1 transitions.     

Components of depolarization-induced transmembrane ion current in isolated smooth muscle cells of the guinea pigtaenia coli

Transmembrane ion currents in isolated single smooth muscle cells (SMC) from the guinea pigtaenia coli were investigated using a whole-cell mode of the patch-clamp technique. Currents induced by depolarizing shifts in the membrane potential from its holding level of −60 mV contained an initial inward phase (Ca²⁺ current), which in 30–40 msec was followed by an outward phase. It was shown that outward current was carried by K ions and consisted at least of three components: one Ca²⁺-independent K⁺ current of delayed rectifier (KV) and two Ca²⁺-dependent K⁺ currents. The latter can be further divided into the apamin-sensitive (SK) and charybdotoxin-sensitive (BK) currents. It was found that relative contributions of these three components in total outward current at 0 mV were 35–45%, 5–15%, and 45–55% for KV, SK, and BK currents, respectively. A potential-dependent current carried by Ci ions was also found. This Cl⁻ current had inward direction within the range of potentials below the chloride equilibrium potential (E _Cl) and outward direction above theE _Cl. The magnitude of Cl⁻ current was significantly lower than the magnitude of total K⁺ current.     

Persistent reflection underlies ectopic activity in multiple sclerosis: a numerical study

Ectopic activity in multiple sclerosis (MS) patients has been traditionally attributed to hyperexcitability of the demyelinated axon segments. Here, we propose that the same outcome may be the result of persistent reflection—the continuous reactivation of the axonal nodes that limit a demyelinated internodal segment. Using computer simulations, we studied the patterns of impulse propagation for a wide range of electrophysiological conditions. In uniformly myelinated fibers, increasing the temperature enabled successful propagation with no blocks in more severe conditions of demyelination. Secondary activations that were originated at the paranodes were formed for temperatures lower than T = 305 K, and at the condition of high sodium channel excitability. Non-sustained and persistent reflections appeared in the case of focally demyelinated fibers, and only within a narrow range of parameters of high temperature and membrane excitability. Persistent reflection reached steady state in ionic currents within 4 ms, and was characterized with a very high activation frequency of 1.504 ± 0.039 kHz. We conclude that persistent reflection is a possible mechanism for ectopic activity in MS patients, being more prominent in higher temperatures and severe axonal demyelination. Eliminating these symptoms may be addressed by cooling the body or by applying pharmacological agents to alter excitability properties.     

Fast activation of a time-dependent outward current in protoplasts derived from coats of developing Phaseolus vulgaris seeds

An outward current that appeared to activate instantaneously in response to depolarising voltage pulses at low sampling frequencies predominated in the plasma membrane of ground-parenchyma protoplasts derived from coats of developing Phaseolus vulgaris L. (cv. Redland Pioneer) seeds. However, the outward current showed time-dependent activation when higher sampling frequencies were used to measure the current. Activation of the current was best described as a double-exponential time course with the fast and slow time constants being 1 and 20 ms, respectively. The current also exhibited a rapid deactivation that followed a double-exponential time course with time constants of approximately 2 and 30 ms, respectively. “Tail-current” analysis allowed us to show that this current exhibited a low selectivity between K⁺ and Cl⁻ (P _K:Cl=1.8). Such a fast-activating current may account for some of the reports of time-independent, instantaneous currents that have been observed in plasma membranes of plant cells digitised at low sampling frequencies. Therefore, when “instantaneous” currents appear it is advisable to characterise these currents using higher sampling frequencies with correspondingly higher filtering frequency cut-offs. Received: 12 May 2000 / Accepted: 26 June 2000     

Functional characterization of voltage-gated K+ channels in mouse pulmonary artery smooth muscle cells

Mice are useful animal models to study pathogenic mechanisms involved in pulmonary vascular disease. Altered expression and function of voltage-gated K⁺ (K_V) channels in pulmonary artery smooth muscle cells (PASMCs) have been implicated in the development of pulmonary arterial hypertension. K_V currents (I_K(V)) in mouse PASMCs have not been comprehensively characterized. The main focus of this study was to determine the biophysical and pharmacological properties of I_K(V) in freshly dissociated mouse PASMCs with the patch-clamp technique. Three distinct whole cell I_K(V) were identified based on the kinetics of activation and inactivation: rapidly activating and noninactivating currents (in 58% of the cells tested), rapidly activating and slowly inactivating currents (23%), and slowly activating and noninactivating currents (17%). Of the cells that demonstrated the rapidly activating noninactivating current, 69% showed I_K(V) inhibition with 4-aminopyridine (4-AP), while 31% were unaffected. Whole cell I_K(V) were very sensitive to tetraethylammonium (TEA), as 1 mM TEA decreased the current amplitude by 32% while it took 10 mM 4-AP to decrease I_K(V) by a similar amount (37%). Contribution of Ca²⁺-activated K⁺ (K_Ca) channels to whole cell I_K(V) was minimal, as neither pharmacological inhibition with charybdotoxin or iberiotoxin nor perfusion with Ca²⁺-free solution had an effect on the whole cell I_K(V). Steady-state activation and inactivation curves revealed a window K⁺ current between –40 and –10 mV with a peak at –31.5 mV. Single-channel recordings revealed large-, intermediate-, and small-amplitude currents, with an averaged slope conductance of 119.4 ± 2.7, 79.8 ± 2.8, 46.0 ± 2.2, and 23.6 ± 0.6 pS, respectively. These studies provide detailed electrophysiological and pharmacological profiles of the native K_V currents in mouse PASMCs. K_V channels     

A Tunable Ultra-Broadband Metamaterial Absorber with Multilayered Structure

In this article, we demonstrate a tunable ultra-broadband metamaterial absorber (TUMA) in terahertz (THz) band which is based on the multilayered structure composed of an Au reflective layer, polyimide dielectric layers, and vanadium dioxide (VO₂) periodic structures, respectively. We gain the tunable absorption spectra because of the room temperature phased-changed character of VO2. The relative bandwidth reaches to 81.2% and the absorption rate is over 90% at the frequency range of 1.63–3.86 THz when the temperature (t₁) is 350 K, but when t₁ = 300 K, the presented absorber is acted as a reflector whose absorption is small besides the frequency points of 9.75 THz and 9.81 THz. For the sake of comprehending the physical mechanism in-depth, the electric field (E-field) diagrams, the surface current distributions and the power loss density (PLD) of the TUMA are investigated. The influences of structural arguments and incident angle (θ) on the absorption are also analyzed. The emulated consequences show that the absorption spectrum can be regulated by changing structural parameters and incident angle and the tunable absorption regions can be obtained by altering the external temperature.

     

Synergic Effects of β-Estradiol and Erythromycin on hERG Currents

The incidence rates of long QT syndrome (LQTS) and drug-induced torsades de pointes (TDP) are higher in women than men. Although gonadal steroids are assumed to play an important role in the gender-based differences in cardiac electrophysiological properties, the underlying mechanisms of the gender-based differences are not fully understood. In particular I _Kr, which comprises the repolarization phase of the action potential, has not been well understood in its modulation by sex hormones. To assess this, we examined the effects of the female sex hormone β-estradiol on the human ether-a-go-go-related gene (hERG)-encoded potassium current stably expressed in human embryonic kidney-293 (HEK) cells. We demonstrated that hERG currents were inhibited by β-estradiol maximally to 62% of control with an IC₅₀ of 1.3 μM and a Hill coefficient of 0.87, which might account for the sex-related differences in LQTS. We also examined whether estrogen modulated drug-induced blocking effects on hERG currents or not. With simultaneous application of 10 μM erythromycin, which is known to block hERG currents but not in low doses, the blocking effects of β-estradiol on hERG currents were enhanced. Namely, hERG currents were inhibited maximally to 45.8% of control with an IC₅₀ of 59 nM (P < 0.02) by β-estradiol with 10 μM erythromycin. We conclude here that a significant block of hERG currents by β-estradiol may account for the sex-related differences in LQTS and the synergic effects of β-estradiol and erythromycin indicate a higher risk of drug-induced TDP in women than men.     

Modulating effect of dopamine on amplitude of GABA-produced chemocontrolled currents in multipolar spinal cord neurons of ammocaete

By using the patch-clamp method in the whole cell configuration, modulating effect of dopamine on GABA-activated currents has been studied on isolated multipolar spinal cord neurons of the ammocaete (larva of the lamprey Lampetra planeri). At application of dopamine (5 μM), there was observed in some cases a decrease of the GABA-activated current, on average, by 33.3 ± 8.7% (n = 8, p < 0.01), in other cases—an increase of the amplitude, on average, by 37.3 ± 11.8% (n = 5, p < 0.01). Concentration of GABA amounted to 2 mM. Study of action of agonists of D1- and D2-receptors on amplitude of chemocontrolled currents has shown that agonist of D1-receptors (+)-SKF-38393 (5 μM) decreases the GABA-activated current amplitude, on average, by 63.1 ± 11.7% (n = 8, p s< 0.01); the agonist of D2-receptors (−)-quinpirole (5 μM) produces in various cells the dopamine-like effects: an increase of the GABA-activated current amplitude, on average, by 61.0 ± 13.8% (n = 8, p < 0.01) and a decrease of amplitude, on average, by 55.7 ± 2.0% (n = 6, p < 0.01). It has been shown that antagonist of D2-receptors sulpiride (5 μM) does not block effects produced by dopamine. The dopamine effects were partially blocked by antagonist of D1-receptors (+)-SCH-23390 (5 μM): a decrease of the GABA-activated amplitude current amounted, on average, to 11.7 ± 1.8% (n = 7, p < 0.01), while an increase of amplitude—8.3 ± 2.0% (n = 5, p < 0.01). At the same time, effects of agonist of D1-receptors quinpirole (5 μM) were partially blocked by antagonist of D1-receptors (+)-SCH-23390: a decrease of the GABA-activated current amplitude amounted, on average, to 9.2 ± 3.4% (n = 6, p < 0.01) and an increase of amplitude—6.3 ± 1.8% (n = 10, p < 0.01). The obtained data indicate differences of mechanisms of the receptor-mediated effect of agonists of dopamine receptors on GABA-activated and potential-activated currents of multipolar neurons of the ammocaete spinal cord.     

Silicon isotope fractionation in rice plants, an experimental study on rice growth under hydroponic conditions

Silicon (Si) isotope composition and Si distribution among different rice plant organs and different parts of rice leaf at maturity were studied, which may provide new insights into the mechanism of Si accumulation in plants and biogeochemical Si cycle. An isotope ratio mass spectrometer (IRMS) was used to examine Si isotope fractionation by rice plant grown in a hydroponic system. The observed ³⁰Si-depletion (about 0.3‰) of whole plant relative to external nutrient solutions suggested biologically mediated Si isotope fractionation occurred during uptake. However, it was not possible to judge the Si uptake mechanism with the data. For δ³⁰Si variation within plant, there was a consistent increasing trend from lower to upper tissues (stem < leaf < husk < grain; leaf sheath < leaf blade base <leaf blade middle < leaf blade top). The phenomenon, reflecting kinetic isotope effects, could be explained that isotope fractionation during Si deposition in rice plant was a Rayleigh-like behavior. The range (−2.7‰ to 2.3‰) of δ³⁰Si variation among rice plant tissues in present experiment exceeded that (−1.7‰ to 2.5‰) of phytoliths observed previously in continents, which would enhance understanding the role of phytoliths on globe Si isotope balance.     

Direct block of cloned hKv1.5 channel by cytochalasins, actin-disrupting agents

The action of cytochalasins, actin-disrupting agents on human Kv1.5 channel (hKv1.5) stably expressed in Ltk^– cells was investigated using the whole cell patch-clamp technique. Cytochalasin B inhibited hKv1.5 currents rapidly and reversibly at +60 mV in a concentration-dependent manner with an IC₅₀ of 4.2 µM. Cytochalasin A, which has a structure very similar to cytochalasin B, inhibited hKv1.5 (IC₅₀ of 1.4 µM at +60 mV). Pretreatment with other actin filament disruptors cytochalasin D and cytochalasin J, and an actin filament stabilizing agent phalloidin had no effect on the cytochalasin B-induced inhibition of hKv1.5 currents. Cytochalasin B accelerated the decay rate of inactivation for the hKv1.5 currents. Cytochalasin B-induced inhibition of the hKv1.5 channels was voltage dependent with a steep increase over the voltage range of the channel's opening. However, the inhibition exhibited voltage independence over the voltage range in which channels are fully activated. Cytochalasin B produced no significant effect on the steady-state activation or inactivation curves. The rate constants for association and dissociation of cytochalasin B were 3.7 µM/s and 7.5 s^–1, respectively. Cytochalasin B produced a use-dependent inhibition of hKv1.5 current that was consistent with the slow recovery from inactivation in the presence of the drug. Cytochalasin B (10 µM) also inhibited an ultrarapid delayed rectifier K⁺ current (I_K,ur) in human atrial myocytes. These results indicate that cytochalasin B primarily blocks activated hKv1.5 channels and endogenous I_K,ur in a cytoskeleton-independent manner as an open-channel blocker. voltage-gated K⁺ channel; heart; open channel block     

Ionic currents in cardiac myocytes of squid, Alloteuthis subulata

This paper provides the first study of voltage-sensitive membrane currents present in heart myocytes from cephalopods. Whole cell patch clamp recordings have revealed six different ionic currents in myocytes freshly dissociated from squid cardiac tissues (branchial and systemic hearts). Three types of outward potassium currents were identified: first, a transient outward voltage-activated A-current (I_A), blocked by 4-aminopyridine, and inactivated by holding the cells at a potential of −40 mV; second, an outward, voltage-activated, delayed rectifier current with a sustained time course (I_K); and third, an outward, calcium-dependent, potassium current (I_K(Ca)) sensitive to Co²⁺ and apamin, and with the characteristic N-shaped current voltage relationship. Three inward voltage-activated currents were also identified. First, a rapidly activating and inactivating, sodium current (I_Na), blocked by tetrodotoxin, inactivated at holding potentials more positive than −40 mV, and abolished when external sodium was replaced by choline. Second, an L-type calcium current (I_Ca,L) with a sustained time course, suppressed by nifedipine or Co²⁺, and enhanced by substituting Ca²⁺ for Ba²⁺ in the external medium. The third inward current was also carried by calcium ions, but could be distinguished from the L-type current by differences in its voltage dependence. It also had a more transient time course, was activated at more negative potentials, and resembled the previously described low-voltage-activated, T-type calcium current. Accepted: 24 September 1999     

A new approach to normalize myocardial temperature in the open-chest pig model

To prevent unphysiological temperaturefluctuations in the myocardium in the open-chest model, we constructeda thermocage. Five pigs under pentobarbital sodium anesthesia underwentrepetitive left anterior descending (LAD) coronary arteryocclusions. Myocardial temperature was measured without any thoracictemperature-controlling device and in the presence of either a heatinglamp or the thermocage. Without any thoracic temperature-controllingdevice, the temperature at 5-mm myocardial depth was 1.28 ± 0.33°C below the intra-abdominal temperature(P < 0.05). During a proximal 5-minLAD occlusion, myocardial temperature decreased by 1.86 ± 1.02°C in the ischemic area (P < 0.05). Both the heating lamp and the thermocage abolished thedifference between intra-abdominal and myocardial temperatures andprevented the decrease in myocardial temperature duringischemia. Only the thermocage minimized myocardial temperaturefluctuations due to air currents and prevented epicardial exsiccation.We conclude that either a thermocage or a heating lamp may be used tonormalize myocardial temperature in the open-chest pig model. However,the thermocage is superior to the lamp in minimizing temperaturefluctuations and preventing epicardial exsiccation.

     

Swelling and Ca2+-activated Anion Conductances in C127 Epithelial Cells Expressing WT and ΔF508-CFTR

CFTR is a chloride channel that is required for fluid secretion and salt absorption in many exocrine epithelia. Mutations in CFTR cause cystic fibrosis. CFTR expression influences some ion channels, but the range of channels influenced, the mechanism of the interaction and the significance for cystic fibrosis are not known. Possible interactions between CFTR and other ion channels were studied in C127 mouse mammary epithelial cell lines stably transfected with CFTR, ΔF508-CFTR, or vector. Cell lines were compared quantitatively using an ¹²⁵I efflux assay and qualitatively using whole-cell patch-clamp recording. As expected, ¹²⁵I efflux was significantly increased by forskolin only in the CFTR line, and forskolin-stimulated whole-cell currents were time- and voltage independent. All three lines responded to hypotonic challenge with large ¹²⁵I efflux responses of equivalent magnitude, and whole-cell currents were outwardly rectified and inactivated at positive voltages. Unexpectedly, basal ¹²⁵I efflux was significantly smaller in the ΔF508-CFTR cell line than in either the CFTR or control cell lines (P < 0.0001), and the magnitude of the efflux response to ionomycin was largest in the vector cell line and smallest in the cell line expressing ΔF508-CFTR (P < 0.01). Whole-cell responses to ionomycin had a linear instantaneous I-V relation and activated at depolarizing voltages. Forskolin responses showed simple summation with responses to ionomycin or hypotonic challenge. Thus, we found no evidence for interactions between CFTR and the channels responsible for swelling-mediated responses. Differences were found in basal and ionomycin-stimulated efflux, but these may arise from variations in the clonally selected cell lines that are unrelated to CFTR expression. Received: 15 November 1995/Revised: 16 February 1996     

HERG1 Currents in Native K562 Leukemic Cells

The human ether-a-go-go related gene (HERG1) K⁺ channel is expressed in neoplastic cells, in which it was proposed to play a role in proliferation, differentiation and/or apoptosis. K562 cells (a chronic myeloid leukemic human cell line) express both the full-length (herg1a) and the N-terminally truncated (herg1b) isoforms of the gene, and this was confirmed with Western blots and coimmunoprecipitation experiments. Whole-cell currents were studied with a tail protocol. Seventy-eight percent of cells showed a HERG1-like current: repolarization to voltages negative to −40 mV produced a transient peak inward tail current, characteristic of HERG1 channels. Cells were exposed to a HERG-specific channel blocker, E4031. Half-maximal inhibitory concentration (IC₅₀) of the blocker was 4.69 nm. The kinetics of the HERG1 current in K562 cells resembled the rapid component of the native cardiac delayed rectifier current, known to be conducted by heterotetrameric HERG1 channels. Fast and slow deactivation time constants at −120 mV were 27.5 and 239.5 ms, respectively. Our results in K562 cells suggest the assembling of heterotetrameric channels, with some parameters being dominated by one of the isoforms and other parameters being intermediate. Hydrogen peroxide was shown to increase HERG1a K⁺ current in heterologous expression systems, which constitutes an apoptotic signal. However, we found that K562 HERG1 whole-cell currents were not activated by H₂O₂.     

Effect of physical factors on the distribution of filamentous green algae in the Tama River

 The distribution of stream-specific filamentous green algae (SSFG) was investigated in the middle reach of the Tama River, Japan. Cladophora glomerata (L.) Kützing and Stigeoclonium sp. dominated among five taxa of SSFG collected in the riverbed with fast currents. These two species were abundant in shallow (<20 cm) riffles with high current velocity (>30 cm s⁻¹), a habitat characterized by high light intensity and extensive aeration. SSFG biomass fluctuated greatly (range, 1.2–85.3 cm² m⁻²), exhibiting no clear seasonal trend. The tufts of SSFG grown on riffle cobbles decreased rapidly when these cobbles were transferred to habitats with either deep water, low current velocity, or both. Laboratory experiments revealed that aeration retarded the decrease in SSFG in incubation vessels. These results suggest that the turbulent conditions of riffle habitats are important for the growth and survival of SSFG in the Tama River. Received: September 5, 2001 / Accepted: April 25, 2002     

Excitation-Contraction Coupling in Crayfish

High-sensitivity recording techniques demonstrate a continuousrelation between the onset and magnitude ot tension and themembrane depolarization that is induced by increasing K in thebathing medium or by intracellularly applied outward currents.This finding is not consistent with the mechanism of signallinge-c coupling by electrotonic spread of a "critical" depolarizationinward along the membrane of the transverse tubular system.It is in accord, however, with the channelled current mechanismthat is based on the known anion-permselectivity of the membranein the terminals of the TTS. The channelled-current model alsopredicts a direct role of Cl and a possible interaction betweenCa and CI in e-c coupling. The initiation and maintenance oftension as well as its magnitude, are in fact dependent uponthe concentrations of Ca and Cl in the medium. Thus, both thesignalling to, and the activation of, the contractile systemappear to be performed by a flow of current in the loop: cellmembrane – cell interior – TTS membrane –TTS channels – exterior, as is envisaged in the channelled-currentmodel of e-c coupling.     

Fluid Recirculation in Necturus Intestine and the Effect of Alanine

Previous studies in our laboratory have shown that Na absorption across the porcine endometrium is stimulated by PGF_2α and cAMP-dependent activation of a barium-sensitive K channel located in the basolateral membrane of surface epithelial cells. In this study, we identify and characterize this basolateral, barium-sensitive K conductance. Porcine uterine tissues were mounted in Ussing chambers and bathed with KMeSO₄ Ringer solution. Amphotericin B (70 μm) was added to the luminal solution to permeabilize the apical membrane and determine the current-voltage relationship of the basolateral K conductance after activation by 100 μm CPT-cAMP. An inwardly rectifying current was identified which possessed a reversal potential of −53 mV when standard Ringer solution was used to bathe the serosal surface. The K:Na selectivity ratio was calculated to be 12:1. Administration of 5 mm barium to the serosal solution completely inhibited the current activated by cAMP under these conditions. In addition to these experiments, amphotericin-perforated whole cell patch clamp recordings were obtained from primary cultures of porcine surface endometrial cells. The isolated cells displayed an inwardly rectifying current under basal conditions. This current was significantly stimulated by CPT-cAMP and blocked by barium. These results together with our previous studies demonstrate that cAMP increases Na absorption in porcine endometrial epithelial cells by activating an inwardly rectifying K channel present in the basolateral membrane. Similar patch clamp experiments were conducted using cells from a human endometrial epithelial cell line, RL95-2. An inwardly rectifying current was also identified in these cells which possessed a reversal potential of −56 mV when the cells were bathed in standard Ringer solution. This current was blocked by barium as well as cesium. However, the current from the human cells did not appear to be activated by cAMP, indicating that distinct subtypes of inwardly rectifying K channels are present in endometrial epithelial cells from different species. Received: 6 February 1997/Revised: 10 July 1997     

Properties of "creep currents" in single frog atrial cells

Changes in membrane current in response to an elevation of [Na]i were studied in enzymatically dispersed frog atrial cells. Na loading by either intracellular dialysis or exposure to the Na ionophore monensin produces changes in membrane current that resemble the "creep currents" originally observed in cardiac Purkinje fibers during exposure to low-K solutions. Na loading induces a transient outward current during depolarizing voltage-clamp pulses, followed by an inward current in response to repolarization back to the holding potential. In contrast to cardiac Purkinje fibers, Na loading of frog atrial cells induces creep currents without accompanying transient inward currents. Creep currents induced by Na loading are insensitive to K channel antagonists like Cs and 4-aminopyridine; they are not influenced by doses of Ca channel antagonists that abolish iCa, but are sensitive to changes in [Ca]o or [Na]o. A comparison of the time course of development of inward creep currents are not tail currents associated with iCa. Inward creep currents can also be induced by experimental interventions that increase the iCa amplitude. Exposure to isoproterenol enhances the iCa amplitude and induces inward creep currents; both can be attenuated by Ca channel antagonists. Both inward and outward creep currents are blocked by low doses of La, independently of La's ability to block iCa. It is concluded that (a) creep currents are not mediated by voltage-gated Na, Ca, or K channels or by an electrogenic Na,K pump; (b) inward creep currents induced either by Na loading or in response to an increase in the amplitude of iCa are triggered by an elevation of [Ca]i; and (c) creep currents may be generated by either an electrogenic Na/Ca exchange mechanism or by a nonselective cation channel activated by [Ca]i.     

Micellar oleic and eicosapentaenoic acid but not linoleic acid influences the β-carotene uptake and its cleavage into retinol in rats

Improving the bioavailability of β-carotene is vital to manage vitamin A deficiency. The influence of micellar oleic (OA), linoleic (LA) and eicosapentaenoic (EPA) acids on plasma β-carotene response and its conversion to retinol has been studied in rats employing single (9 h time course) and repeated (10 days) dose administrations. After a single dose, the levels (area under the curve) of plasma β-carotene and retinyl palmitate in OA and EPA groups were higher (p < 0.05) by 13, 7 and 11, 6 folds than LA group. The liver β-carotene level in OA and EPA groups were higher (p < 0.05) by 3 and 1.2 folds than LA group. After repeated dose, the plasma β-carotene and retinyl palmitate levels in OA (6.2%, 51.7%) and EPA (25.4%, 17.23%) groups were higher (p < 0.05) than LA group. The liver β-carotene level in OA (21.2%) and EPA (17.6%) groups were higher (p < 0.05) than LA group. In both the experiments, the activity of β-carotene 15,15′-dioxygenase in the intestinal mucosa and plasma triglyceride levels were also higher in OA and EPA groups than LA group. β-Carotene excreted through urine and feces of OA and EPA groups was lower than the LA group. These results demonstrate an improved absorption and metabolism of β-carotene when fed mixed micelles with OA or EPA compared with LA. Although the mechanism involved in selective absorption of fatty acids needs further studies, intestinal β-carotene uptake and its conversion to vitamin A can be modulated using specific fatty acids.