Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin

Small-conductance Ca2+-activated K+ channels (SK channels) are independent of voltage and gated solely by intracellular Ca2+. These membrane channels are heteromeric complexes that comprise pore-forming alpha-subunits and the Ca2+-binding protein calmodulin (CaM). CaM binds to the SK channel through the CaM-binding domain (CaMBD), which is located in an intracellular region of the alpha-subunit immediately carboxy-terminal to the pore. Channel opening is triggered when Ca2+ binds the EF hands in the N-lobe of CaM. Here we report the 1.60 A crystal structure of the SK channel CaMBD/Ca2+/CaM complex. The CaMBD forms an elongated dimer with a CaM molecule bound at each end; each CaM wraps around three alpha-helices, two from one CaMBD subunit and one from the other. As only the CaM N-lobe has bound Ca2+, the structure provides a view of both calcium-dependent and -independent CaM/protein interactions. Together with biochemical data, the structure suggests a possible gating mechanism for the SK channel.     

Crystalline ion beams

By freezing out the motion between particles in a high-energy storage ring, it should be possible to create threads of ions, offering research opportunities beyond the realm of standard accelerator physics. The usual heating due to intra-beam collisions should completely vanish, giving rise to a state of unprecedented brilliance. Despite a continuous improvement of beam cooling techniques, such as electron cooling and laser cooling, the ultimate goal of beam crystallization has not yet been reached in high-energy storage rings. Electron-cooled dilute beams of highly charged ions show liquid-like order with unique applications. An experiment using laser cooling suggested a reduction of intra-beam heating, although the results were ambiguous. Here we demonstrate the crystallization of laser-cooled Mg+ beams circulating in the radiofrequency quadrupole storage ring PALLAS at a velocity of 2,800 m s-1, which corresponds to a beam energy of 1 eV. A sudden collapse of the transverse beam size and the low longitudinal velocity spread clearly indicate the phase transition. The continuous ring-shaped crystalline beam shows exceptional stability, surviving for more than 3,000 revolutions without cooling.     

Interaction of sulfonylurea with the pancreatic B-cell

Conclusions Sulfonylureas have a variety of effects on pancreatic B-cells. In the present review an attempt has been made to identify those that appear fundamental from a mechanistic point of view and in that sense common to all hypoglycemic drugs tested. On several points the available able experimental information is limited. With this reservation in mind, the following general hypothesis is presented for the insulin-releasing action of this class of drugs. Hypoglycemic sulfonylureas and related [(acylamino)alkyl]benzoic acids bind to the B-cell plasma membrane, a step in which hydrophobic anchoring is essential. Dissociated acidic COOH or SO₂NHCO groups in the drugs are thus presented to an ion-gating protein in the plasma membrane, possibly in the vicinity of a pair of sulfur atoms. The reduced state of these sulfurs is promoted, preventing the formation of a disulfide bridge. K⁺ permeability is thereby decreased, favoring depolarization of the B-cell and Ca²⁺ influx through voltage-dependent channels. Finally, Ca²⁺ triggers the physiological apparatus for discharge of the insulin secretory granules. The effect of this insulinreleasing signal chain is amplified by cyclic AMP which increases in the B-cell as a consequence of depolarization and Ca²⁺ influx. This hypothesis does not attribute an ionophoretic role to the sulfonylureas per sebecause various experiments with cells and artificial membrane systems render such an idea apparently less tenable.     

Isolation and some properties of the heparin-neutralizing factor (PF4) released from human blood platelets

Zusammenfassung Der in Form eines hochmolekularen Komplexes von den Plättchen freigesetzte, heparinneutralisierende Faktor (PF 4) konnte reversibel in ein Träger-Material und ein aktives Protein (Molekulargewicht ca. 30000) aufgespalten werden.

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This work was supported by the Schweizerischer Nationalfonds zur Förderung der wissenschaftlichen Forschung.     

Drosophila enzyme-genetics: A table

Summary A method for the vacuum distillation of microgram amounts of substances is described.     

Effect of cerium on drug metabolizing activity in rat liver

Zusammenfassung Es wird gezeigt, dass i.v. injiziertes Cerium (2 mg/kg) eine hemmende Wirkung auf den Stoffwechsel von Arzneien in der Rattenleber hat.     

A new method for measuring membrane potentials with external electrodes

Zusammenfassung Beschreibung einer neuen Methode, die es gestattet, mit Aussenelektroden die wahre Grösse der Membranpotentialschwankungen, die durch den Einfluss von hyper- oder hypopolarisierenden Substanzen oder durch die Erregung in markhaltigen Nervenfasern erzeugt werden, zu registrieren.     

The histamine and heparin content of the rat's mesenterial mast cells regenerating after application of compound 48/80

Zusammenfassung Der Histamin- und Heparingehalt in Mastzellen, die nach totaler Zerstörung mit Histaminliberator 48/80 regenerieren, wird untersucht. Die Ergebnisse zeigen, dass während des Regenerationsprozesses die Anzahl der Mastzellen, in denen sich das Histamin mit Reineckesalzlösung anfärbt, kleiner ist, als die Anzahl der Mastzellen, die mit Toluidinblau darzustellen sind.     

Die Genomsonderung in den Mitosen der Rattenleber

Summary Model squashes with gelatine cubes containing 8 files like the chromosomes ofBellevalia romana (2n=8) showed the chromosomes only in groupings that correspond to the original position of metaphase chromosomes. The metaphase chromosomes in root tip cells ofBellevalia romana are arranged at random; there is neither somatic pairing nor genome segregation (= grouping of metaphase chromosomes into two complete chromosome sets). In contradiction to these results, the chromosomes in the regenerating liver cells (2n=42) show a certain precentage of grouping into complete genomes. It is concluded that in rat liver cells a mechanism exists which, starting with the genome segregation, may produce a change in chromosome number. Thus these same euploid or aneuploid chromosome numbers can be explained which are really observed in normal and treated rat liver. 4 possibilities of such mechanism are discussed.

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Nach einem Vortrag, gehalten anlässlich des IV. Symposium histologicum internationale Lausanne (Suisse), 5.–8. September 1961.