Roles and regulation of the cardiac sodium channel Nav1.5: Recent insights from experimental studies

During the past decade, Nav1.5, the main voltage-gated Na+ channel in the heart, has been shown to be involved in many cardiac diseases. Genetic variants in the gene SCN5A, encoding Nav1.5, have been linked to various cardiac phenotypes, such as the congenital and acquired long QT syndromes, Brugada syndrome, conduction slowing, sick sinus syndrome, atrial fibrillation, and even cases of dilated cardiomyopathy. This unexpected phenotypic diversity may reflect that Nav1.5 is not only restricted to the initiation of the action potential and rapid cardiac conduction, but may also be involved in other, not-yet elucidated, functions. Despite the fact that our understanding of the regulation of expression, localization, and function of Nav1.5 is deepening, we are still far from a comprehensive view. Much of our current knowledge has been obtained by carrying out experiments using "cellular expression systems”, e.g. host cells expressing exogenous Nav1.5. Although very informative, these techniques are limited, in that Nav1.5 is not expressed in the physiological cellular environment of a cardiac cell. Recently, however, there have been several studies published which used approaches closer to "normal” or pathological physiology. In an attempt to summarize recently published data, this article will review the phenotypes of genetically-modified mouse strains where Nav1.5 expression and activity are directly or indirectly modified, as well as the regulation of Nav1.5 function using native cardiac myocytes. Despite obvious limitations, the reviewed studies provide an overview of the complex multi-factorial and multi-protein regulation of Nav1.

Dracula’s Brides: Economic Seclusion, Prostitution, and Domestic Neglect

Bram Stoker's Dracula accrued International recognition and acclaim and is the foundation of an expansive creative outpour of literature, film adaptations, and numerous interpretations. The name Dracula is familiar around the world and has been critiqued by numerous schools of thought. The paper looks at the Bram Stoker's use of female vampires to highlight the New Woman, economic dependence, and domestic neglect

On the Stereochemistry of the Lone-Pair Electrons in AX6E-Systems: Dynamically Distorted Anion in (NH4)2SeBr6, Statically Distorted Anion in l, 3-Propanediammonium-Hexabromoselenate(IV) (C3N2H12)SeBr6

Using 293 K diffractometer intensity data, the crystal structures of (NH4)2SeBr6 (1) and [H3N(CH2)3NH3]SeBr6 (2) have been determined by single crystal X-ray technique and refined to a final Rw of 0.049 and 0.040, respectively. The dark red crystals of 1 are cubic (space group Fm3m) with a = 10.478(2) Å and Z = 4. This structure contains SeBe62- octahedra (point symmetry m3̄m, distance Se-Br: 2.577(2) Å in an antifluorite type arrangement of cations and anions. In contrast, the SeBr fi 2-ion in 2 is statically distorted (approximate point symmetry 3m, distance Se-Br min. 2,547(2), max. 2.595(2) Å. The dark red crystals are orthorhombic (space group Pnma) with a = 17.795(3), b = 7.5037(6), c = 10.476(1) Å and Z = 4. The results agree with the rules for the appearance of a static/dynamic stereochemical effect of the lone pair electrons given for TeX62- (X = Cl, Br, I) species (W. Abriel, Acta Crystallogr. B 42, 449 (1986)). Consequently these rules can be extended considering SeX62- as well. Basic structural data for all compounds containing AX62- ions (A = Se, Te; X = Cl, Br, I) known to date are given including the ⊿-values (R. D. Shannon, Acta Crystallogr. A 32, 751 (1976)) as a measure for the distortion of the octahedral anion

Darstellung und Kristallstruktur von [H3N(CH2)3NH3]SbCl5

Using 293 K diffractometer intensity data, the structure of [H3N(CH2)3NH3]SbCl5 has been determined by single crystal X-ray technique and refined to a final Rw of 0.026. The colorless crystals are monoclinic (space group P21/c) with a = 10.1338(5), b = 11.4623(7), c = 11.3668(6) Å, β = 113.52(5)° and Ζ = 4. The structure contains ψ-octahedral SbCl52- anions. A center of symmetry connects two anions forming a (Sb2Cl10)4- unit with rather long Sb—Cl distances for the bridging Cl-atoms (2.92 and 3.68 A, respectively)

Die Kristallstrukturen von Verbindungen des Typs A2TeX6 (A = K, NH4, Rb, Cs; X = Cl, Br, I)

With the determination of the crystal structure of (NH4)2TeI6 the list of the descriptions of A2TeX6 structures is further completed. At 293 K three structure types are observed with an antifluorite packing of cations and anions: The cubic K2PtCl6 type structure (space group Fm 3̄ m, Z = 4), the tetragonal Rb2TeI6 type structure (space group P4/mnc, Z = 2), and the monoclinic K2TeBr6 type structure (space group P21/n, Z = 2). The latter type was found for (NH4)2TeI6 with a = 8.0694(7), b = 8.0926(9), c = 11.7498(8) Å and β = 89.605(8)° and refined to a final Rw of 0.065. From ionic radii ratios the symmetry of the A2MX6 type structures can be predicted including a prediction of low temperature instability (soft mode condensation). Group-subgroup relationships connect the corresponding space groups and the space groups of the high/low temperature polymorphs

Zur Stereochemie des freien Elektronenpaares in AX6E-Systemen, VIII Statisch verzerrte Anionen in [H3N(CH2)3NH3]3(BiX6)2(H2O)2 mit X = Cl, Br

Using 293 K diffractometer intensity data, the crystal structures of [H3N(CH2)3NH3]3(BiX6)2(H2O)2 with X - Cl, Br have been determined by single crystal X-ray technique and refined to a final Rw of 0.027 and 0.043, respectively. The structures are isotypic, space group P21/c, Z = 2 with a = 14.415(1). b = 9.7401(7), c = 12.4609(9)Å, β = 105.997(8)°for X - Cl and a = 14.794(2), b = 10.127(2), c = 12.853(2)Å, β = 105.68(2)° for X - Br. Statically distorted BiX63- octahedra confirm the symmetry rules for the stereochemistry of the lone pair electrons in AX6E-systems. Basic structural data for all compounds containing BiX63- and SbXh3 ions (X = Cl, Br, I) known to date are given including the ⊿-values as a measure for the distortion of the octahedral coordination polyhedron

Vibronische Kopplung und dynamisch verzerrte Strukturen in Hexahalogenotelluraten(IV): Ergebnisse aus Tieftemperatur-Röntgenbeugungsuntersuchungen (300—160 K) und aus FTIR-spektroskopischen Experimenten (300—5 K) [1]

From theoretical considerations a dynamically distorted octahedron as a result of vibronic coupling between the ground state and the first excited state should exist for 14 electron AX6E systems like TeX62- . A high symmetry crystal field yielding at least a center of symmetry for the Te position stabilizes this fluctuating structure, otherwise statical distortion will be observed. From X-ray diffraction experiments on antifluorite type compounds A2TeX6 (A = Rb. Cs: X = Cl, Br) the averaged structure (m3̅m symmetry) of the anions was found even at very low temperatures. The thermal parameters are not significantly different from those of similar SnX62 compounds. Distortions therefore are very small and are evident from FTIR spectroscopic meas­urements only. Here very broad T1u-deformation vibration bands are observed down to tempera­tures <10 K without splitting: Astatically distorted species could not be frozen out. In contrast to XeF6 for TeX62- the energy gap between the threefold, fourfold or sixfold minima of the potential surface (according to the symmetry of one component of the T1u-vibration) is very small and shifted to temperatures lower than reached with the devices used for these experiments