Interdomain Interactions Control Ca2+-Dependent Potentiation in the Cation Channel TRPV4

Several Ca2+-permeable channels, including the non-selective cation channel TRPV4, are subject to Ca2+-dependent facilitation. Although it has been clearly demonstrated in functional experiments that calmodulin (CaM) binding to intracellular domains of TRP channels is involved in this process, the molecular mechanism remains elusive. In this study, we provide experimental evidence for a comprehensive molecular model that explains Ca2+-dependent facilitation of TRPV4. In the resting state, an intracellular domain from the channel N terminus forms an autoinhibitory complex with a C-terminal domain that includes a high-affinity CaM binding site. CaM binding, secondary to rises in intracellular Ca2+, displaces the N-terminal domain which may then form a homologous interaction with an identical domain from a second subunit. This represents a novel potentiation mechanism that may also be relevant in other Ca2+-permeable channels

Divinylphenylene- and Ethynylvinylphenylene-Bridged Mono-, Di-, and Triruthenium Complexes for Covalent Binding to Gold Electrodes

International audienceIn this work, we describe the preparation and the properties of the novel bis(vinylphenylene)-bridged diruthenium complexes {Ru(CO)(η2-O2C-p-C6H4SAc)(PiPr3)2}2(μ-CH═CH-C6H4-CH═CH-1,3 and -1,4) (6 and 7), the bis(ethynylphenylene)-bridged complex trans-[AcS-p-C6H4-C≡C-Ru(dppe)2-C≡C-p-C6H4-C≡C-Ru(dppe)2-C≡C-p-C6H4-SAc] (11), the bis(1-ethynyl-4-vinylphenylene)-bridged triruthenium complex trans-[{Ru(dppe)2}{−C≡C-p-C6H4-CH═CH-Ru(CO)(η2-O2C-p-C6H4SAc)(PiPr3)2}2] (8), and the monometallic congeners Ru(CH═CH-p-C6H4SAc)(CO)(η2-O2C-p-C6H4SAc)(PiPr3)2 (4) and trans-[Ru(dppe)2(−C≡C-p-C6H4-SAc)2] (10). These mono-, bi-, and trimetallic complexes feature terminal acetyl-protected thiol functions for covalent binding to gold surfaces or for bridging the gaps of gold nanoelectrodes. All complexes display low oxidation potentials, and IR studies of the neutral complex 8 and of its various oxidized forms 8n+ indicate the high vinyl/ethynyl bridging ligand contribution to the oxidation processes and complete charge delocalization in all available oxidation states (n = 1–3). Strong delocalization of the relevant occupied frontier MOs over the entire π-conjugated {Ru}–bridge–{Ru′}–bridge–{Ru} backbone is also supported by DFT calculations on the parent complexes V8 and V8OMe. The benzoate ligand bearing the functional group for gold binding is outside the conjugation path and insulates the wirelike central portion of these molecules from their periphery. Upon insertion into molecular junctions, these molecules are expected to enhance sequential tunneling and to facilitate Coulomb blockade behavior. They will thus contribute to our understanding of structure–property relationships for metal-containing molecular wires

Divinylphenylene- and Ethynylvinylphenylene-Bridged Mono‑, Di‑, and Triruthenium Complexes for Covalent Binding to Gold Electrodes

In this work, we describe the preparation and the properties of the novel bis­(vinylphenylene)-bridged diruthenium complexes {Ru­(CO)­(η²-O₂C-<i>p-</i>C₆H₄SAc)­(P^<i>i</i>Pr₃)₂}₂(μ-CHCH-C₆H₄-CHCH-1,3 and -1,4) (<b>6</b> and <b>7</b>), the bis­(ethynylphenylene)-bridged complex <i>trans</i>-[AcS-<i>p</i>-C₆H₄-CC-Ru­(dppe)₂-CC-<i>p</i>-C₆H₄-CC-Ru­(dppe)₂-CC-<i>p</i>-C₆H₄-SAc] (<b>11</b>), the bis­(1-ethynyl-4-vinylphenylene)-bridged triruthenium complex <i>trans</i>-[{Ru­(dppe)₂}­{−CC-<i>p</i>-C₆H₄-CHCH-Ru­(CO)­(η²-O₂C-<i>p-</i>C₆H₄SAc)­(P^<i>i</i>Pr₃)₂}₂] (<b>8</b>), and the monometallic congeners Ru­(CHCH-<i>p</i>-C₆H₄SAc)­(CO)­(η²-O₂C-<i>p-</i>C₆H₄SAc)­(P^<i>i</i>Pr₃)₂ (<b>4</b>) and <i>trans</i>-[Ru­(dppe)₂(−CC-<i>p</i>-C₆H₄-SAc)₂] (<b>10</b>). These mono-, bi-, and trimetallic complexes feature terminal acetyl-protected thiol functions for covalent binding to gold surfaces or for bridging the gaps of gold nanoelectrodes. All complexes display low oxidation potentials, and IR studies of the neutral complex <b>8</b> and of its various oxidized forms <b>8</b>^{<b><i>n</i>+</b>} indicate the high vinyl/ethynyl bridging ligand contribution to the oxidation processes and complete charge delocalization in all available oxidation states (<i>n</i> = 1–3). Strong delocalization of the relevant occupied frontier MOs over the entire π-conjugated {Ru}–bridge–{Ru′}–bridge–{Ru} backbone is also supported by DFT calculations on the parent complexes <b>V8</b> and <b>V8</b>_<b>OMe</b>. The benzoate ligand bearing the functional group for gold binding is outside the conjugation path and insulates the wirelike central portion of these molecules from their periphery. Upon insertion into molecular junctions, these molecules are expected to enhance sequential tunneling and to facilitate Coulomb blockade behavior. They will thus contribute to our understanding of structure–property relationships for metal-containing molecular wires

Work-Life-Balance: Diskurse, Problemlagen, Forschungsperspektiven

Oechsle M. Work-Life-Balance: Diskurse, Problemlagen, Forschungsperspektiven. In: Becker R, Kortendiek B, eds. Handbuch Frauen- und Geschlechterforschung. Geschlecht und Gesellschaft. Vol 35. 2., erw. und aktualisierte. Wiesbaden: VS Verlag für Sozialwissenschaften; 2008: 227-236