The low KM-phosphodiesterase inhibitor denbufylline enhances neuronal excitability in guinea pig hippocampus in vitro

The actions of the phosphodiesterase inhibitor denbufylline on the excitability of hippocampal neurons were investigated by means of extracellular and intracellular recordings. Denbufylline, which has been shown to selectively inhibit a low KM, Ca2+/calmodulin-independent phosphodiesterase isozyme, concentration-dependently increased the amplitude of the extracellularly recorded CAI population spike evoked by electrical stimulation of the Schaffer collateral/commissural pathway. Concentration-response-curves yielded an EC50 for denbufylline of 0.76 M. In comparison, the nonselective phosphodiesterase inhibitor 3-isobutyl-lmethylxanthine (IBMX) also produced an increase in the amplitude of the population spike. From the concentration-response-curve, which was steeper than that of denbufylline, an EC50 for IBMX of 1.04 M was obtained. However, despite their similar EC50 values, denbufylline was found to be significantly more potent at lower concentrations (<- 300 nM) than IBMX. Intracellular recordings from CAI pyramidal cells revealed postsynaptic actions of denbufylline (300 nM) as indicated by a small drug-induced depolarization (2 – 5 mV) associated with an increase in membrane input resistance by 10–20%. In addition, denbufylline blocked the accommodation of trains of action potentials evoked by the injection of depolarizing current pulses. The results suggest i) that accumulation of adenosine-3,5-monophosphate (CAMP) in the postsynaptic cell and/or in the presynaptic terminal produced by blockade of phosphodiesterases leads to enhanced synaptic transmission in the CAI area of the hippocampus and ii) that a low KM, Ca 2+/calmodulin-independent cAMP-phosphodiesterase is an important component involved in the regulation of the intracellular cAMP level at synapses of central nervous system neurons

Lithium distribution across the membrane of motoneurons in the isolated frog spinal cord

Lithium sensitive microelectrodes were used to investigate the transmembrane distribution of lithium ions (Li+) in motoneurons of the isolated frog spinal cord. After addition of 5 mmol·l–1 LiCl to the bathing solution the extracellular diffusion of Li+ was measured. At a depth of 500 m, about 60 min elapsed before the extracellular Li+ concentration approached that of the bathing solution. Intracellular measurements revealed that Li+ started to enter the cells soon after reaching the motoneuron pool and after up to 120 min superfusion, an intra — to extracellular concentration ratio of about 0.7 was obtained. The resting membrane potential and height of antidromically evoked action potentials were not altered by 5 mmol·l–1 Li+

Ultra-thin corrugated metamaterial film as large-area transmission dynode

Large-area transmission dynodes were fabricated by depositing an ultra-thin continuous film on a silicon wafer with a 3-dimensional pattern. After removing the silicon, a corrugated membrane with enhanced mechanical properties was formed. Mechanical materials, such as this corrugated membrane, are engineered to improve its strength and robustness, which allows it to span a larger surface in comparison to flat membranes while the film thickness remains constant. The ultra-thin film consists of three layers (Al$_2$O$_3$ /TiN/Al$_2$O$_3$) and is deposited by atomic layer deposition (ALD). The encapsulated TiN layer provides in-plane conductivity, which is needed to sustain secondary electron emission. Two types of corrugated membranes were fabricated: a hexagonal honeycomb and an octagonal pattern. The latter was designed to match the square pitch of a CMOS pixel chip. The transmission secondary electron yield was determined with a collector-based method using a scanning electron microscope. The highest transmission electron yield was measured on a membrane with an octagonal pattern. A yield of 2.15 was achieved for 3.15 keV incident electrons for an Al$_2$O$_3$ /TiN/Al$_2$O$_3$ tri-layer film with layer thicknesses of 10/5/15 nm. The variation in yield across the surface of the corrugated membrane was determined by constructing a yield map. The active surface for transmission secondary electron emission is near 100%, i.e. a primary electron generates transmission secondary electrons regardless of the point of impact on the corrugated membrane

Presynaptic actions of 4-Aminopyridine and γ-aminobutyric acid on rat sympathetic ganglia in vitro

Responses to bath-applications of 4-aminopyridine (4-AP) and -aminobutyric acid (GABA) were recorded intracellularly from neurones in the rat isolated superior cervical ganglion. 4-aminopyridine (0.1–1.0 mmol/l) usually induced spontaneous action potentials and excitatory postsynaptic potentials (EPSPs), which were blocked by hexamethonium. Membrane potential was unchanged; spike duration was slightly increased. Vagus nerve B-and C-fibre potentials were prolonged. In 4-AP solution (0.1–0.3 mmol/l), GABA (0.1 mmol/l), 3-aminopropanesulphonic acid or muscimol evoked bursts of spikes and EPSPs in addition to a neuronal depolarization. These bursts, which were not elicited by glycine, glutamate, taurine or (±)-baclofen, were completely antagonised by hexamethonium, tetrodotoxin or bicuculline methochloride. It is concluded that: (a) 4-AP has a potent presynaptic action on sympathetic ganglia; (b) presynaptic actions of GABA can be recorded postsynaptically in the presence of 4-AP; and (c) the presynaptic GABA-receptors revealed in this condition are similar to those on the postsynaptic membrane

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Baade-Wesselink distances and the effect of metallicity in classical cepheids

The aim of this paper is to investigate the metallicity dependence of the $PL$-relation in $V$ and $K$ based on a sample of 68 Galactic Cepheids with individual Baade-Wesselink distances (some of the stars also have an HST-based parallax) and individually determined metallicities from high-resolution spectroscopy. Literature values of the $V$-band, $K$-band and radial velocity data have been collected for a sample of 68 classical cepheids that have their metallicity determined in the literature from high-resolution spectroscopy. Based on a $(V-K)$ surface-brightness relation and a projection factor derived in a previous paper, distances have been derived from a Baade-Wesselink analysis. $PL$- and $PLZ$-relations in $V$ and $K$ are derived. The effect of the adopted dependence of the projection factor on period is investigated. The change from a constant $p$-factor to one recently suggested in the literature with a mild dependence on $\log P$ results in a less steep slope by 0.1 unit, which is about the 1-sigma error bar in the slope itself. The observed slope in the $PL$-relation in $V$ in the LMC agrees with both hypotheses. In $K$ the difference between the Galactic and LMC slope is larger and would favour a mild period dependence of the $p$-factor. The dependence on metallicity in $V$ and $K$ is found to be marginal, and independent of the choice of $p$-factor on period. This result is severely limited by the small range in metallicity covered by the Galactic Cepheids.Comment: A&A accepte