Adenoviral expression of IKs contributes to wavebreak and fibrillatory conduction in neonatal rat ventricular cardiomyocyte monolayers

Previous studies have shown that the gating kinetics of the slow component of the delayed rectifier K(+) current (I(Ks)) contribute to postrepolarization refractoriness in isolated cardiomyocytes. However, the impact of such kinetics on arrhythmogenesis remains unknown. We surmised that expression of I(Ks) in rat cardiomyocyte monolayers contributes to wavebreak formation and facilitates fibrillatory conduction by promoting postrepolarization refractoriness. Optical mapping was performed in 44 rat ventricular myocyte monolayers infected with an adenovirus carrying the genomic sequences of KvLQT1 and minK (molecular correlates of I(Ks)) and 41 littermate controls infected with a GFP adenovirus. Repetitive bipolar stimulation was applied at increasing frequencies, starting at 1 Hz until loss of 1:1 capture or initiation of reentry. Action potential duration (APD) was significantly shorter in I(Ks)-infected monolayers than in controls at 1 to 3 Hz (P<0.05), whereas differences at higher pacing frequencies did not reach statistical significance. Stable rotors occurred in both groups, with significantly higher rotation frequencies, lower conduction velocities, and shorter action potentials in the I(Ks) group. Wavelengths in the latter were significantly shorter than in controls at all rotation frequencies. Wavebreaks leading to fibrillatory conduction occurred in 45% of the I(Ks) reentry episodes but in none of the controls. Moreover, the density of wavebreaks increased with time as long as a stable source sustained the fibrillatory activity. These results provide the first demonstration that I(Ks)-mediated postrepolarization refractoriness can promote wavebreak formation and fibrillatory conduction during pacing and sustained reentry and may have important implications in tachyarrhythmias.

Time-dependent interactions of the two porphyrinic compounds chlorin e6 and mono-L-aspartyl-chlorin e6 with phospholipid vesicles probed by NMR spectroscopy

The distribution processes of chlorin e6 (CE) and monoaspartyl-chlorin e6 (MACE) between the outer and inner phospholipid monolayers of 1,2-dioleoyl-phosphatidylcholine (DOPC) vesicles were monitored by 1H NMR spectroscopy through analysis of chemical shifts and line widths of the DOPC vesicle resonances. Chlorin adsorption to the outer vesicle monolayer induced changes in the DOPC 1H NMR spectrum. Most pronounced was a split of the N-methyl choline resonance, allowing for separate analysis of inner and outer vesicle layers. Transbilayer distribution of the chlorin compounds was indicated by time-dependent characteristic spectral changes of the DOPC resonances. Kinetic parameters for the flip-flop processes, that is, half-lives and rate constants, were obtained from the experimental data points. In comparison to CE, MACE transbilayer movement was significantly reduced, with MACE remaining more or less attached to the outer membrane layer. The distribution coefficients for CE and MACE between the vesicular and aqueous phase were determined. Both CE and MACE exhibited a high affinity for the vesicular phase. For CE, a positive correlation was found between transfer rate and increasing molar ratio CE/DOPC. Enhanced membrane rigidity induced by increasing amounts of cholesterol into the model membrane was accompanied by a decrease of CE flip-flop rates across the membrane. The present study shows that the movement of porphyrins across membranes can efficiently be investigated by 1H NMR spectroscopy and that small changes in porphyrin structure can have large effects on membrane kinetics.

Electrochemical characterization of self-assembled Ferrocene-terminated alkanethiol monolayers on low-index gold single crystal electrodes

We present a voltammetric and in situ STM study of 11-ferrocenyl-1-undecanethiol (FcC11) assembled on low-index single crystal and polycrystalline gold electrodes. The influence of electrode surface structure as well as of structure defects in the self-assembled FcC11 monolayers on the electrochemical response during the oxidation and reduction of the terminal ferrocene group is explored. The nature of the redox peaks is discussed in detail. We identified the coexistence of disordered FcC11 regions with 2D patches of “locally ordered” FcC11 species. We demonstrate that close-packed domains are preferentially formed at atomically flat terraces. Increasing the defect density of the substrate surface leads to a decreasing amount of locally ordered FcC11 molecules.

Ferrocene-terminated alkanethiol self-assembled monolayers: An electrochemical and in situ surface-enhanced infra-red absorption spectroscopy study

The effect of anions on the redox behavior and structure of 11-ferrocenyl-1-undecanethiol (FcC11) monolayers (SAM) on Au(1 1 1) single crystal and Au(1 1 1-25 nm) thin film electrodes was investigated in 0.1 M solutions of HPF6, HClO4, HBF4, HNO3, and H2SO4 by cyclic voltammetry (CV) and in situ surface-enhanced infrared reflection-absorption spectroscopy (SEIRAS). We demonstrate that the FcC11 redox peaks shift toward positive potentials and broaden with increasing hydrophilicity of the anions. In situ surface-enhanced IR-spectroscopy (SEIRAS) provided direct access for the incorporation of anions into the oxidized adlayer. The coadsorption of anions is accompanied by the penetration of water molecules. The latter effect is particularly pronounced in aqueous HNO3 and H2SO4 electrolytes. The adlayer permeability increases with increasing hydrophilicity of the anions. We also found that even the neutral (reduced) FcC11 SAM is permeable for water molecules. Based on the property of interfacial water to reorient upon charge inversion, we propose a spectroscopic approach for estimating the potential of zero total charge of the FcC11-modified Au(1 1 1) electrodes in aqueous electrolytes.

Relativistic current collection by a cylindrical Langmuir probe

The current I to a cylindrical Langmuir probe with a bias Φp satisfying β≡eΦp/mec2∼O(1) is discussed. The probe is considered at rest in an unmagnetized plasma composed of electrons and ions with temperatureskTe∼kTi≪mec2. For small enough radius, the probe collects the relativistic orbital-motion-limited (OML) current I OML , which is shown to be larger than the non-relativistic result; the OML current is proportional to β1/2 and β3/2 in the limits β≪1 and β≫1, respectively. Unlike the non-relativistic case, the electron density can exceed the unperturbed density value. An asymptotic theory allowed to compute the maximum radius of the probe to collect OML current, the sheath radius for probe radius well below maximum and how the ratio I/I OML drops below unity when the maximum radius is exceeded. A numerical algorithm that solves the Vlasov-Poisson system was implemented and density and potential profiles presented. The results and their implications in a possible mission to Jupiter with electrodynamic bare tethers are discussed density value. An asymptotic theory allowed to compute the maximum radius of the probe to collect OML current, the sheath radius for probe radius well below maximum and how the ratio I/IOML drops below unity when the maximum radius is exceeded. A numerical algorithm that solves the Vlasov-Poisson system was implemented and density and potential profiles presented. The results and their implications in a possible mission to Jupiter with electrodynamic bare tethers are discussed.

Interference of parallel cylindrical Langmuir probes

Current to a cylindrical probe of arbitrary cross section is discussed. Previous results for circular cylinders at the high bias and moderate radius R of interest for electrodynamic bare tethers, for which space charge may be ignored over a large neighborhood of the probe, depend in separate ways on both R and perimeter p. These results are extended to a general convex cross section by introducing certain equivalent radius Req. For any concave cross section, results use a proper equivalent perimeter peq , in addition to Req. Finally, for the joint cross section of separate parallel probes, certain effective perimeter peff replaces peq. Rules to determine Req. peq. and peff are used to discuss collection interference among two or more parallel cylinders when brought from far away to contact

Ion-temperature-sensitive effect in transient langmuir probe response

A theory is presented for a method, recently proposed by Hester and Sonin, of determining the ion temperature in a plasma by measuring the transient current to a cylindrical Langmuir probe after applying a potential Vp{ — eVpy>KTe) under conditions where collection is collision free and the ratio of probe radius to Debye length is small. The ion component of the current does not approach its final steady-state value monotonicalfy, but exhibits a strong, ion-temperature-dependent overshoot in the first few ion-plasma periods following the biasing of the probe. Analytical formulas are derived for the case of a Maxwellian plasma, and convenient graphical results are presented. The possible masking of the overshoot by a transient displacement current is discussed; it is shown how to avoid such displacement effects. For the overshoot to be sensitive to the ion temperature T the probe must be near plasma (zero) potential before applying V1,(eVp~<0.lKTe, VP~ being that initial potential); this is not a drawback of the method, but, on the contrary, it can be used to accurately determine plasma potential along with T.

The orbital-motion-limited regime of cylindrical Langmuir probes

An asymptotic analysis of electron collection at high bias Fp serves to determine the domain of validity of the orbital-motion-limited regime of cylindrical Langmuir probes, which is basic for the workings of conductive bare tethers. The radius of a wire collecting OML current in an unmagnetized plasma at rest cannot exceed a value, Rmax , which is found to exhibit a minimum as a function of Fp ; atFp values of interest, Rmax is already increasing and is larger than the electron Debye length lDe . The breakdown of the regime relates to conditions far fromthe probe, at electron energies comparable to the ion thermal energy, kTi ; Rmax is found to increase with Ti . It is also found that ~1! the maximumwidth of a thin tape, if used instead of a wire, is 4Rmax ; ~2! the electron thermal gyroradius must be larger than both R and lDe for magnetic effects to be negligible; and ~3! conditions applying to the tether case are such that trapped-orbit effects are negligible.