Movement Of Counterions Research Articles

Arrhythmic Intracellular Ca2+ Signaling and Electrocardiogram in the Heart of the TRIC-A-/- Mice

Trimeric intracellular cation (TRIC) channel subtypes are present in the endo/sarcoplasmic reticulum (SR) of muscle, heart and other tissues, which contribute to the movement of counter ions associated with the rapid release of Ca2+ from intracellular stores (Yazawa et al., Nature 448: 78–82). We recently showed that skeletal muscle derived from the TRIC-A knockout mice develop overload of Ca2+ inside the SR that leads to instability of ryanodine receptor (RyR1)-mediated Ca2+ release and muscle contraction (Zhao et al., JBC, 285: 37370-6). Here we examine the function of TRIC-A in regulation of Ca2+ signaling in the cardiac muscle. Cardiomyocytes isolated from the TRIC-A knockout mice show reduced Ca2+ spark frequency under resting condition. Ca2+ transients in response to voltage stimulation display arrhythmic patterns compared with the wild type controls. While electrocardiogram (ECG) of TRIC-A knockout mice reveal minor arrhythmic patterns under resting condition, infusion of isoproterenol (80 mg/kg) leads to drastic and acute elevation of arrhythmic ECG patterns that are rarely seen in the wild type mice. Chronic treatments with isoproterenol (60 mg/kg/day for 14 days) induce development of cardiac hypertrophy and fibrosis that are significantly more evident in the TRIC-A knockout mice compared with the wild type controls. Biochemical studies show that the major Ca2+ regulatory proteins in the cardiac muscle, e.g. RyR2, NCX, SERCA, Cav1.2 and JP2 are not changed. Our data suggest an important role for TRIC-A in regulation of Ca2+ signaling in heart function. Since the absence of TRIC-A caused overload of Ca2+ inside the SR, the stress-induced arrhythmic Ca2+ signaling and ECG of the TRIC-A knockout heart could reflect the store-overload induced Ca2+ release mechanism, which has been demonstrated for the RyR2 Ca2+ release channel in the cardiac muscle.

TRIC-A Channels in Vascular Smooth Muscle Contribute to Blood Pressure Maintenance

TRIC channel subtypes, namely TRIC-A and TRIC-B, are intracellular monovalent cation channels postulated to mediate counter-ion movements facilitating physiological Ca(2+) release from internal stores. Tric-a-knockout mice developed hypertension during the daytime due to enhanced myogenic tone in resistance arteries. There are two Ca(2+) release mechanisms in vascular smooth muscle cells (VSMCs); incidental opening of ryanodine receptors (RyRs) generates local Ca(2+) sparks to induce hyperpolarization, while agonist-induced activation of inositol trisphosphate receptors (IP(3)Rs) evokes global Ca(2+) transients causing contraction. Tric-a gene ablation inhibited RyR-mediated hyperpolarization signaling to stimulate voltage-dependent Ca(2+) influx, and adversely enhanced IP(3)R-mediated Ca(2+) transients by overloading Ca(2+) stores in VSMCs. Moreover, association analysis identified single-nucleotide polymorphisms (SNPs) around the human TRIC-A gene that increase hypertension risk and restrict the efficiency of antihypertensive drugs. Therefore, TRIC-A channels contribute to maintaining blood pressure, while TRIC-A SNPs could provide biomarkers for constitutional diagnosis and personalized medical treatment of essential hypertension.

THE EFFECT OF CARBON FILLER TYPE ON ACTUATION BEHAVIOR OF CONDUCTING POLYMER ACTUATOR

Conducting polymer (CP) actuators undergo a volume change as the redox state is changed. The volume change is caused by the movement of counter ions into the film during the electrical oxidation process. In freestanding CP actuators, the electrical resistance of a CP film can produce significant power-supply voltage (IR) drop along its length, which can restrict the actuator performance. To solve this problem, CP nanocomposite with carbon filler was introduced. This study aimed to improve conductivity and ease off the IR drop occurred during the actuation of CP actuator. CP nanocomposite actuator with 3:7 of CB:CNF co-filler content showed the maximum displacement due to the synergy effect, and did not involve IR drop when the length of actuator was 25 mm.

TRIC-A Channel and Blood Pressure Regulation

Trimeric intracellular cation (TRIC) channel subtypes, namely TRIC-A and TRIC-B, function as intracellular channels conducting monovalent cations throughout tissues and probably mediate counter-ion movements coupled with Ca2+ release from the endo/sarcoplasmic reticulum. Knockout mice lacking both TRIC-A and TRIC-B channels suffer embryonic cardiac failure, and the mutant cardiomyocytes display severe dysfunction in SR Ca2+ handling (Yazawa et al., Nature, 2007). In knockout mice lacking TRIC-B channels with neonatal lethality due to respiratory failure, alveolar epithelial cells exhibit compromised Ca2+ release and thus insufficiently produce and secret surfactant phospholipids (Yamazaki et al., Development, 2009). The observations indicate that TRIC channels act as counter-ion channels functionally coupled with Ca2+ release in various cell types.Here we report the direct linkage of TRIC channels with hypertension. Knockout mice lacking TRIC-A channels showed significant hypertension and bradycardia. Ca2+ channel antagonists, but not blockers for vasoactive agents, exerted antihypertensive effects in the mutant mice. Moreover, despite retaining normal passive diameters in a Ca2+-free bathing solution, the mutant arteries showed narrow diameter results from higher resting Ca2+ level maintained by Ca2+ influx via L-type Ca2+ channel. In vascular smooth muscle cells (VSMCs), spontaneous opening of ryanodine receptor channels generates local Ca2+ release called Ca2+ sparks, activates cell-surface Ca2+-dependent K+ channels and reduces membrane potential toward relaxation. Our physiological and pharmacological studies suggested that the loss of TRIC-A channels compromises Ca2+ spark and spontaneous transient outward currents (STOCs) generation. In membrane potential monitoring using the voltage-dependent dye, the mutant VSMCs exhibited elevated resting membrane potential and prolonged repolarizing phases after high KCl-induced depolarization. These results suggested that the loss of TRIC-A in VSMCs enhanced the basal tonus induced by higher resting Ca2+ level results from decrease of Ca2+ sparks, STOCs frequency and depolarization of membrane potential.

Ca2+ Overload and Sarcoplasmic Reticulum Instability in tric-a Null Skeletal Muscle

The sarcoplasmic reticulum (SR) of skeletal muscle contains K(+), Cl(-), and H(+) channels may facilitate charge neutralization during Ca(2+) release. Our recent studies have identified trimeric intracellular cation (TRIC) channels on SR as an essential counter-ion permeability pathway associated with rapid Ca(2+) release from intracellular stores. Skeletal muscle contains TRIC-A and TRIC-B isoforms as predominant and minor components, respectively. Here we test the physiological function of TRIC-A in skeletal muscle. Biochemical assay revealed abundant expression of TRIC-A relative to the skeletal muscle ryanodine receptor with a molar ratio of TRIC-A/ryanodine receptor ∼5:1. Electron microscopy with the tric-a(-/-) skeletal muscle showed Ca(2+) overload inside the SR with frequent formation of Ca(2+) deposits compared with the wild type muscle. This elevated SR Ca(2+) pool in the tric-a(-/-) muscle could be released by caffeine, whereas the elemental Ca(2+) release events, e.g. osmotic stress-induced Ca(2+) spark activities, were significantly reduced likely reflecting compromised counter-ion movement across the SR. Ex vivo physiological test identified the appearance of "alternan" behavior with isolated tric-a(-/-) skeletal muscle, i.e. transient and drastic increase in contractile force appeared within the decreasing force profile during repetitive fatigue stimulation. Inhibition of SR/endoplasmic reticulum Ca(2+ ATPase) function could lead to aggravation of the stress-induced alternans in the tric-a(-/-) muscle. Our data suggests that absence of TRIC-A may lead to Ca(2+) overload in SR, which in combination with the reduced counter-ion movement may lead to instability of Ca(2+) movement across the SR membrane. The observed alternan behavior with the tric-a(-/-) muscle may reflect a skeletal muscle version of store overload-induced Ca(2+) release that has been reported in the cardiac muscle under stress conditions.

Influence of Cyclosporine A on Molecular Interactions in Lyotropic Reverse Hexagonal Liquid Crystals

We present a dielectric study of H(II) mesophases (H(II)) based on a GMO/tricaprylin/phosphatidylcholine/water system seeded with the peptide Cyclosporine A (CSA). The study covers a frequency range 0.01 Hz to 1 MHz and a temperature range of 293 to 319 K, with a 3 K temperature step. Three dielectric relaxation processes are observed and discussed. This picture is further elucidated by comparison with a dielectric study of the empty H(II) mesophase system, previously published, where the same three processes were involved. A complex picture emerges whereby the CSA is intercalated between the surfactant tails yet protrudes into the interface as well. Whereas the CSA remains hydrophobic, it still influences the relaxation behavior of the GMO head and counterion movement along the interface in a nontrivial manner. The third dipolar species, the tricaprylin molecule, is also influenced by the presence of CSA. A critical temperature T(0) = 307 K is recognized and identified as the dehydration temperature of the surfactant heads. This induces a conformal transition in the CSA, drastically changing its effect on the three dielectric processes evident in the raw data. The implications of this behavior are discussed in detail.

Essential role of the TRIC-B channel in Ca2+ handling of alveolar epithelial cells and in perinatal lung maturation

TRIC channels function as monovalent cation-specific channels that mediate counter ion movements coupled with ryanodine receptor-mediated Ca(2+) release from intracellular stores in muscle cells. Mammalian tissues differentially contain two TRIC channel subtypes: TRIC-A is abundantly expressed in excitable cells, whereas TRIC-B is ubiquitously expressed throughout tissues. Here, we report the physiological role of TRIC-B channels in mouse perinatal development. TRIC-B-knockout neonates were cyanotic owing to respiratory failure and died shortly after birth. In the mutant neonates, the deflated lungs exhibited severe histological defects, and alveolar type II epithelial cells displayed ultrastructural abnormalities. The metabolic conversion of glycogen into phospholipids was severely interrupted in the mutant type II cells, and surfactant phospholipids secreted into the alveolar space were insufficient in the mutant neonates. Moreover, the mutant type II cells were compromised for Ca(2+) release mediated by inositol-trisphosphate receptors, despite Ca(2+) overloading in intracellular stores. Our results indicate that TRIC-B channels take an active part in Ca(2+) signalling to establish specialised functions in type II cells and are thus essential for perinatal lung maturation.

Probing Flow Velocity with Silicon Nanowire Sensors

We report our experimental efforts to quantify the impact of fluidic and ionic transport on the conductance level of silicon nanowire (SiNW) sensors configured as field effect transistors (FETs). Specifically, the conductance of SiNW FETs placed in a microfluidic channel was observed to change linearly with the flow velocity of electrolytic solutions. The direction of conductance change depends on the doping type of the SiNWs and their location inside the microfluidic channel, and the magnitude of the conductance change varies with the ionic strength and compositions of the electrolytic solution. Our quantitative analysis suggests that the flow velocity sensing is a consequence of the streaming potential that is generated by the movement of counterions inside the electrical double layer (EDL) of the silica substrate. The streaming potential, which varies with the flow velocity and the ionic properties of the electrolytic solution, acts in the same way as the charged analytes in affecting the conductance of SiNWs by changing the surface potential. This study highlights the importance of considering the ionic transport in analyzing and optimizing nanowire FET sensors, which can significantly change the conductance of NWs. Moreover, SiNWs were demonstrated for the first time to be able to detect the streaming potential, the flow velocity and the ionic strength, opening up their new application potentials in microfluidics.

Conducting Polypyrrole Conical Nanocontainers: Formation Mechanism and Voltage Switchable Property

AbstractNanostructures with stimuli‐responsive properties are of great importance for the application of smart materials in nanotechnology. Unique hollow polypyrrole nanostructured arrays with a conical shape have been produced by a stepwise electropolymerization process. The polypyrrole conical nanocontainers exhibit a reversible switchable behavior between open and closed states, which is controlled by the movement of counter ions during electrically controlled reversible oxidation and reduction processes. The formation of conical nanocontainers is affected by the oleo‐wettability of the substrate. Conical nanocontainers can be formed on oleo‐phobic substrates in aqueous solution by using dopant‐stabilized pyrrole nanodroplets as the guiding template for the polymerization.magnified image

Electrochemistry and spectroelectrochemistry of tert-butylcalix[4]arene bridged bis double-decker lutetium(III) phthalocyanine, Lu 2Pc 4 and dimeric lutetium(III) phthalocyanine, Lu 2Pc 2(OAc) 2

In this study, electrochemical, electrochromic and spectroelectrochemical properties of a tert-butylcalix[4]arene bridged bis double-decker lutetium(III) phthalocyanine (Lu 2Pc 4 2) were investigated explicitly as compared with a tert-butylcalix[4]arene bridged dimeric lutetium(III) phthalocyanine [Lu 2Pc 2(OAc) 2 1]. Distinctive differences between electrochemical and electrochromic properties of 1 and 2 were detected. Moreover, the properties of 1 and 2 were compared with previously reported S 4(CH 2) 4 bridged Lu 2Pc 2(OAc) 2 and Lu 2Pc 4. The calixarene bridged phthalocyanine (Pc) compounds, 1 and 2 showed well-defined electrochromic behaviour with green-blue and blue-purple colour transitions. The enhanced electrochromic properties of 2, as compared to 1, were attributed to its double-decker structure, probably allowing the formation of suitable ion channels for the counter ion movement in the solid film.

Ultrafast Voltammetry for Probing Interfacial Electron Transfer in Molecular Wires

Electron transfer inside self-assembled monolayers made from complex redox-active oligophenylenevinylene molecular wires is examined by ultrafast cyclic voltammetry. Rate constants above 10(6) s(-1) are measured when the electroactive moieties are easily accessible to counterions from the electrolyte. These counterion movements are necessary to compensate the local charge created upon electron transfer. Conversely, if the redox center is buried within long hydrophobic diluents, the counterion movement towards the redox entity becomes rate limiting, thus drastically altering the rate magnitude and its physical meaning. This change in the mechanism is examined both for superexchange or when one electron-hopping step is involved.

Fluid Transport across the Isolated Porcine Ciliary Epithelium

To quantify spontaneous fluid transport across the isolated porcine ciliary epithelium and determine its sensitivity to the electrolyte transport inhibitors ouabain and bumetanide, as well as bath Cl(-) and HCO(3)(-) levels. A complete annulus of ciliary body was mounted in a custom-designed chamber appropriate for quantifying net fluid movement, as well as the transepithelial potential difference (PD) across the in vitro ciliary epithelium. A spontaneous and stable fluid flow (FF) in the blood-to-aqueous direction was measured over a 4-hour period. This flux solely reflected the secretory activity of the isolated ciliary epithelium (CE), given the absence of externally applied osmotic or pressure gradients. In contrast to FF, the PD declined during the 4 hours in vitro, suggesting that the integrity of the tight junctions may have been compromised during this time so that an increased movement of counter ions via the paracellular pathway could have shunted the PD, while at the same time transcellular fluid transport remained unaffected. The FF in the blood-to-aqueous direction (2.3 +/- 0.2 muL/hr; n = 7) was eliminated by a unilateral reduction in the bath Cl(-) levels on the blood side of the preparation and restored on reintroducing the anion to the bathing medium. This linkage between FF and blood side [Cl(-)] is consistent with the existence of a net Cl(-) flux across the porcine CE in the same direction as the fluid transport. Addition of bumetanide to the blood-side bath inhibited FF by approximately 40%, whereas the removal of CO(2)/HCO(3)(-) from the blood-side bathing solution elicited a approximately 50% reduction in FF. Ouabain inhibited the FF from either side of the preparation, although the effects were more rapid when the glycoside was applied to the blood side of the tissue. Overall, these findings indicate the dependence of FF on active ionic transport by the isolated CE. Isolated porcine ciliary epithelial preparations transport fluid in the blood-to-aqueous direction, indicating that measurements of volumetric fluid flow across this preparation may serve as a suitable model for future studies directed toward the pharmacological control of secretion.

Solid-state Conducting Polymer Actuator based on Electrochemically-deposited Polypyrrole and Solid Polymer Electrolyte

Conducting polymer (CP) actuators undergo a volumetric change as their redox state is changed. The volumetric change is due to the movement of counter ions into the film during the electrical oxidation process. Liquid electrolytes are mostly used for the actuation of CP actuators, but that is an impediment for practical use of CP actuator. To overcome this problem, in this study solid polymer electrolyte (SPE) was introduced into the CP actuator instead of electrolyte solution. A polypyrrole (PPy)/SPE/PPy electroactive tri-layer actuator was prepared by the electrochemical polymerization of pyrrole and the actuation characteristics were studied. An all-solid actuator, consisting of two PPy films and a SPE based on polyurethane (PU), clearly showed a reversible displacement in an atmosphere when a voltage was applied.

The Reliability of Relative Anion-Cation Permeabilities Deduced From Reversal (Dilution) Potential Measurements in Ion Channel Studies

Measurements of anion-cation permeability ratios (e.g., PCl/PNa) are most readily made by measuring changes in zero-current reversal potential when the salt concentration on one side of the membrane (e.g., external NaCl) is decreased. This is particularly useful for measuring changes in ion selectivity in wild-type and mutant channels, such as those of the ligand-gated ion channel superfamily, and has shown that many of these channels have a significant permeability to counter-ions. One Brownian dynamics study of ion permeation through such narrow ion channels failed to observe such counter-ion movement, although later, another Brownian dynamics study did observe counter-ion movement through simulations of the same channels. The question has been raised as to the reliability of such reversal potential measurements for determining permeability ratios, particularly given the use of an equation such as the Goldman-Hodgkin-Katz (GHK) equation, which is often used to calculate such ratios. A new derivation of the GHK equation in terms of activity coefficients is also included. The application of irreversible thermodynamics will be shown to qualitatively support the reliability of such experimental anion-cation permeability values derived from reversal potential measurements. It will then be shown that for such zero-current situations, different electrodiffusion models, with very different underlying assumptions, produce almost identical relative permeabilities (and reversal potentials). Finally, the results of the two Brownian dynamics simulation studies and the relationship between reversal potentials and relative permeability will be discussed.

Moving front phenomena in the switching of conductive polymers

Abstract A theoretical analysis of mass transport phenomena in conductive polymer-modified electrodes is presented. In the first part, the electronic transport properties of such polymers are described by two different diffusion coefficients: one relates to the electron mobility in the conductive state, the other describes electronic transport in the non-conductive state. Thus, this approach postulates a discontinuity for the electron diffusion coefficient with the local concentration of oxidized states within the film. It is shown that this hypothesis leads to the concept of a moving front which separates an area where the film is in its conductive state from one where it is in its insulating state. The same conclusions are drawn when D increases steeply with the concentration of oxidized sites, i.e. the doping level of the polymer. Thus, moving front phenomena appear to be intrinsically linked to the specificity of conductive polymers, i.e. the dramatic change in electronic conductivity upon switching. Assuming that the electrochemical process, for a chronoamperometric experiment, is controlled by electron diffusion leads to a front velocity proportional to t −1/2 and to the diffusion coefficient of the electron in the conductive zone. When this coefficient tends towards infinity a contradiction to the assumption of a process controlled by electron movements occurs. In this case, the electrochemical process can be controlled either by counter-ion movements or by the rate of the electrochemical reaction that takes place at the moving boundary; the velocity of the front is not proportional to t −1/2 and the chronoamperometric response can deviate from the usual Cottrell behaviour. In the second part of this work, the counter-ion movement is analysed. It is proposed that the conducting properties of the material might lead to a marked enhancement of the migrational aspect of ion transport within the internal structure of the film. It is then shown that describing ion transport as a migration phenomenon instead of a diffusion phenomenon leads again to the concept of a moving front. Several propagation equations are demonstrated: the first describes the concentration profile of counter-ions and the second describes the potential profile within the film. These two equations indicate that both concentration and electric potential propagate in the material at the same velocity. This velocity is proportional to the driving electric field, i.e. the potential drop that develops at the conductive|insulating interface or within the insulating zone of the material and varies with anion mobility.

Flux−Force Formalism for Charge Transport Dynamics in Supramolecular Structures. 2. Diffusivity and Electroneutrality Coupling Effects

The conductance and transport number expressions are derived for the ion-involved electron-hopping (IIEH) mechanism taking into account the ion pairing between fixed redox ions and the mobile electroinactive counterions. Under the steady-state condition, the effects of ion pairing, the ratio of diffusivity associated with electron hopping and the mobile electroinactive counterion, and the applied potential are studied both in the presence and in the absence of supporting electrolyte. The main effect of ion pairing is to decrease the charge transport rate, and that of the diffusivity rake is to change the mechanism of the conductance process from ohmic (electronic) to redox (or nonohmic). This change in the conductance behavior from ohmic to nonohmic is shown to be due to the change in the rate-limiting process from electron transport to counterion movement. A direct correlation between the proposed theory and experimental results obtained earlier using poly(benzimidazobenzophenanthroline) and [Os(vbpy)3]2+/[Zn(vbpy)3]2+ copolymer coated electrodes is demonstrated.

Resolution of electron and proton transfer events in the electrochromism associated with quinone reduction in bacterial reaction centers

We have measured the electrochromic response of the bacteriopheophytin, BPh, and bacteriochlorophyll, BChl, cofactors during the QA −QB → QAQB − electron transfer in chromatophores of Rhodobacter (Rb.) capsulatus and Rb. sphaeroides. The electrochromic response rises faster in chromatophores and is more clearly biexponential than it is in isolated reaction centers. The chromatophore spectra can be interpreted in terms of a clear kinetic separation between fast electron transfer and slower non-electron transfer events such as proton transfer or protein relaxation. The electrochromic response to electron transfer exhibits rise times of about 4 µs (70%) and 40 µs (30%) in Rb. capsulatus and 4 µs (60%) and 80 µs (40%) in Rb. sphaeroides. The BPh absorption band is shifted to nearly equivalent positions in the QA − and nascent QB − states, indicating that the electrochromic perturbation of BPh absorption from the newly formed QB − state is comparable to that of QA − . Subsequently, partial attenuation of the QB − electrochromism occurs with a time constant on the order of 200 µs. This can be attributed to partial charge compensation by H+ (or other counter ion) movement into the QB pocket. Electron transfer events were found to be slower in detergent isolated RCs than in chromatophores, more nearly monoexponential, and overlap H+ transfer, suggesting that a change in rate-limiting step has occurred upon detergent solubilization.

Calcium uptake and release modulated by counter‐ion conductances in the sarcoplasmic reticulum of skeletal muscle

The sarcoplasmic reticulum (SR) plays the central role in regulating the free myoplasmic Ca2+ level for the contractile activation of skeletal muscle. The initial stages of the voltage-controlled Ca2+ release mechanism are known in molecular detail. However, there is still very little known about the later stages of Ca2+ uptake and total Ca2+ turnover in the contraction-relaxation cycle under normal physiological conditions or under conditions influenced by fatigue or disease. Ca2+ uptake and release are both accompanied by "counter-ion' movements across the SR membrane which prevent or reduce the generation of SR membrane potentials and balance for electroneutrality in the SR lumen. The SR membrane is permeable for the cations K+, Na+, H+ and Mg2+ and the anion Cl-. Using electron-probe X-ray microanalysis. It has been shown that during tetanic stimulation the Ca2+ release was mainly balanced by uptake of K+ and Mg2+ leaving a charge deficit that was assumed to be neutralized via H+ ion or organic counter-ion movement. The low time resolution of electron-probe X-ray microanalysis leaves the possibility of other transient concentration changes in the SR, e.g. for Cl- ions. Possible physiological roles of the SR counter-ion conductances can be tested using skinned muscle fibre preparations with intact sarcoplasmic reticulum and removed or chemically permeabilized outer sarcolemma. In skinned fibres, the SR K+ conductance can be effectively reduced with SR K+ channel blockers such as 4-aminopyridine, tetraethylammonium and decamethonium. Interestingly, these blockers increase Ca2+ loading as well as Ca2+ release, whereas other less specific blockers, such as 1.10-bis-quanidino-n-decane, seem to reduce Ca2+ release, possibly also via blocking Ca2+ release channels. Thus, it seems very important also to test the effects of counter-currents carried by K+, Mg2+, H+ or Cl- ions on intact and voltage-clamped single-fibre preparations.

Adsorption behavior of functionalized ferrocenylalkane thiols and disulfide onto Au and ITO and electrochemical properties of modified electrodes: Effects of acyl and alkyl groups attached to the ferrocene ring

Abstract The effects of introduction of the acyl and alkyl groups into the ferrocene ring on the redox potentials and the adsorption behavior were investigated by studying the electrochemical characteristics of Au and ITO electrodes modified with six novel ferrocenylalkane thiol and disulfide derivatives. On introducing an acyl group into the ferrocene ring, the redox potentials of the modified electrodes in 0.1 M HClO4 shifted in the positive direction by ca. 300 mV per acyl group. This shift is due to the electron-withdrawing effect of the carbonyl group. Introduction of a butyl group into the ring shifted the redox potential about 15 mV in the positive direction, possibly because of steric hindrance of counter-ion movement. The surface concentration of these ferrocene derivatives was estimated from the redox charge of the ferrocene moieties. Both the maximum surface concentration Γmax and the adsorption rate constants kad on Au and ITO decreased as the number of the acyl groups increased. The effect of the butyl group on Γmax and kad was smaller. Both Γmax and kad of the disulfide derivative on Au were smaller than those of the corresponding thiol derivative. Although the redox potentials were the same at the modified Au and ITO electrodes, both Γmax and kad on ITO were much smaller than those on Au.

A membrane potential model with counterions for cytosolic calcium oscillations

An initial model has been proposed to describe a mechanism for cytosolic calcium oscillations [Jafri MS. Vajda S. Pasik P. Gillo B. (1992) A membrane model for cytosolic calcium oscillations: a study using Xenopus oocytes. Biophys. J., 63, 235–246]. In this paper we extend our original model to include the effects of counterion movement Into the ER in response to calcium release. This produces smoother oscillations over a wider parameter range. We have lowered the endoplasmic reticulum (ER) Intraluminal free calcium concentration and shown that the oscillations can occur at lower ER membrane potentials, consistent with physiological values. The improved model is then tested with two representative paradigms that are currently under investigation by many researchers. The model predicts that the reduction of the ER calcium pump (Ca-ATPase) rate can cause the termination of cytosolic calcium oscillations in an active cell, and induce oscillations in a resting cell. This result is consistent with experiments with thapsigargin, a Ca-ATPase activity Inhibitor. In addition, we simulate the latency period for the response to the application of agonist and offer a plausible explanation for it. Our mathematical model Is currently the only model that formulates the contributions of calcium binding proteins, ER membrane potential, ER counterion movements, and distinct calcium pump populations, and describes their effects on cytosolic calcium oscillations.