Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Tetramerization Dynamics of C-terminal Domain Underlies Isoform-specific cAMP Gating in Hyperpolarization-activated Cyclic Nucleotide-gated Channels

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are dually activated by hyperpolarization and binding of cAMP to their cyclic nucleotide binding domain (CNBD). HCN isoforms respond differently to cAMP; binding of cAMP shifts activation of HCN2 and HCN4 by 17 mV but shifts that of HCN1 by only 2-4 mV. To explain the peculiarity of HCN1, we solved the crystal structures and performed a biochemical-biophysical characterization of the C-terminal domain (C-linker plus CNBD) of the three isoforms. Our main finding is that tetramerization of the C-terminal domain of HCN1 occurs at basal cAMP concentrations, whereas those of HCN2 and HCN4 require cAMP saturating levels. Therefore, HCN1 responds less markedly than HCN2 and HCN4 to cAMP increase because its CNBD is already partly tetrameric. This is confirmed by voltage clamp experiments showing that the right-shifted position of V-1/2 in HCN1 is correlated with its propensity to tetramerize in vitro. These data underscore that ligand-induced CNBD tetramerization removes tonic inhibition from the pore of HCN channels

Tetramerization Dynamics of C-terminal Domain Underlies Isoform-specific cAMP Gating in Hyperpolarization-activated Cyclic Nucleotide-gated Channels.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are dually activated by hyperpolarization and binding of cAMP to their cyclic nucleotide binding domain (CNBD). HCN isoforms respond differently to cAMP; binding of cAMP shifts activation of HCN2 and HCN4 by 17 mV but shifts that of HCN1 by only 2-4 mV. To explain the peculiarity of HCN1, we solved the crystal structures and performed a biochemical-biophysical characterization of the C-terminal domain (C-linker plus CNBD) of the three isoforms. Our main finding is that tetramerization of the C-terminal domain of HCN1 occurs at basal cAMP concentrations, whereas those of HCN2 and HCN4 require cAMP saturating levels. Therefore, HCN1 responds less markedly than HCN2 and HCN4 to cAMP increase because its CNBD is already partly tetrameric. This is confirmed by voltage clamp experiments showing that the right-shifted position of V(½) in HCN1 is correlated with its propensity to tetramerize in vitro. These data underscore that ligand-induced CNBD tetramerization removes tonic inhibition from the pore of HCN channels

Inscriptiones latinae liberae rei pubblicae

Si segnalano numerose iscrizioni, edite più ο meno recentemente, suscettibili di entrare a far parte del corpus delle iscrizioni latine di età repubblicana. Di altre, già incluse in CIL, si propone di correggere la datazione, la lettura ο l'interpretazione. Si aggiungono molti altri testi inediti e si indica quali iniziative siano in corso per dotare CIL, I2 di nuovi indici e per tenere aggiornata la raccolta in futuro.Panciera Silvio, Bertinetti Marina, Di Stefano Manzella Ivan, Friggeri Rosanna, Gregori Gian Luca, Ricci Cecilia, Gentili Sara, Vergantini Gloria, Caldelli Maria Letizia, Priuli Stefano, Petrucci Nadia, Sabbatini Tumolesi Patrizia, Baldarotta Donatella, Buroni Marta, Illuminati Anna, Tagliamonte Gianluca, Fora Maurizio, Lega Claudia, Chioffi Laura, Lo Giudice Cristina, Granino Cecere Maria Grazia, Salomies Olii, Solin Heikki, Kajava Mika, Cébeillac-Gervasoni Mireille, Sironen Timo, Volpe Rita, Letta Cesare, Filippi Giorgio, Segenni Simonetta, Sensi Luigi, Mennella Giovanni, Zaccaria Claudio, Krummrey Hans. Inscriptiones latinae liberae rei pubblicae. In: Epigrafia. Actes du colloque international d'épigraphie latine en mémoire de Attilio Degrassi pour le centenaire de sa naissance. Actes de colloque de Rome (27-28 mai 1988) Rome : École Française de Rome, 1991. pp. 241-491. (Publications de l'École française de Rome, 143

Inscriptiones latinae liberae rei pubblicae

Si segnalano numerose iscrizioni, edite più ο meno recentemente, suscettibili di entrare a far parte del corpus delle iscrizioni latine di età repubblicana. Di altre, già incluse in CIL, si propone di correggere la datazione, la lettura ο l'interpretazione. Si aggiungono molti altri testi inediti e si indica quali iniziative siano in corso per dotare CIL, I2 di nuovi indici e per tenere aggiornata la raccolta in futuro.Panciera Silvio, Bertinetti Marina, Di Stefano Manzella Ivan, Friggeri Rosanna, Gregori Gian Luca, Ricci Cecilia, Gentili Sara, Vergantini Gloria, Caldelli Maria Letizia, Priuli Stefano, Petrucci Nadia, Sabbatini Tumolesi Patrizia, Baldarotta Donatella, Buroni Marta, Illuminati Anna, Tagliamonte Gianluca, Fora Maurizio, Lega Claudia, Chioffi Laura, Lo Giudice Cristina, Granino Cecere Maria Grazia, Salomies Olii, Solin Heikki, Kajava Mika, Cébeillac-Gervasoni Mireille, Sironen Timo, Volpe Rita, Letta Cesare, Filippi Giorgio, Segenni Simonetta, Sensi Luigi, Mennella Giovanni, Zaccaria Claudio, Krummrey Hans. Inscriptiones latinae liberae rei pubblicae. In: Epigrafia. Actes du colloque international d'épigraphie latine en mémoire de Attilio Degrassi pour le centenaire de sa naissance. Actes de colloque de Rome (27-28 mai 1988) Rome : École Française de Rome, 1991. pp. 241-491. (Publications de l'École française de Rome, 143