Unanticipated structural and functional properties of delta-subunit-containing GABAA receptors

GABA(A) receptors mediate inhibitory neurotransmission in the mammalian brain via synaptic and extrasynaptic receptors. The delta (delta)-subunit-containing receptors are expressed exclusively extra-synaptically and mediate tonic inhibition. In the present study, we were interested in determining the architecture of receptors containing the delta-subunit. To investigate this, we predefined the subunit arrangement by concatenation. We prepared five dual and three triple concatenated subunit constructs. These concatenated dual and triple constructs were used to predefine nine different GABA(A) receptor pentamers. These pentamers composed of alpha(1)-, beta(3)-, and delta-subunits were expressed in Xenopus oocytes and maximal currents elicited in response to 1 mm GABA were determined in the presence and absence of THDOC (3alpha, 21-dihydroxy-5alpha-pregnane-20-one). beta(3)-alpha(1)-delta/alpha(1)-beta(3) and beta(3)-alpha(1)-delta/beta(3)-alpha(1) resulted in the expression of large currents in response to GABA. Interestingly, the presence of the neurosteroid THDOC uncovered alpha(1)-beta(3)-alpha(1)/beta(3)-delta receptors, additionally. The functional receptors were characterized in detail using the agonist GABA, THDOC, Zn(2+), and ethanol and their properties were compared with those of non-concatenated alpha(1)beta(3) and alpha(1)beta(3)delta receptors. Each concatenated receptor isoform displayed a specific set of properties, but none of them responded to 30 mm ethanol. We conclude from the investigated receptors that delta can assume multiple positions in the receptor pentamer. The GABA dose-response properties of alpha(1)-beta(3)-alpha(1)/beta(3)-delta and beta(3)-alpha(1)-delta/alpha(1)-beta(3) match most closely the properties of non-concatenated alpha(1)beta(3)delta receptors. Furthermore, we show that the delta-subunit can contribute to the formation of an agonist site in alpha(1)-beta(3)-alpha(1)/beta(3)-delta receptors.

Multifunctional Coordination Compounds: Design and Properties

Cleverly designed molecular building blocks provide chemists with the tools of a powerful molecular-scale construction set. They enable them to engineer materials having a predictable order and useful solid-state properties. Hence, it is in the realm of supramolecular chemistry to follow a strategy for synthesizing materials which combine a selected set of properties, for instance from the areas of magnetism, photophysics and electronics. As a successful approach, host/guest solids which are based on extended anionic, homo- and bimetallic oxalato-bridged transition-metal compounds with two-and three-dimensional connectivities have been investigated. In this report, a brief review is given on the structural aspects of this class of compounds followed by a presentation of a thermal and magnetic study for two distinct, heterometallic oxalato-bridged layer compounds.

Flexibility Properties in Complex Analysis and Affine Algebraic Geometry

In the last decades affine algebraic varieties and Stein manifolds with big (infinite-dimensional) automorphism groups have been intensively studied. Several notions expressing that the automorphisms group is big have been proposed. All of them imply that the manifold in question is an Oka–Forstnerič manifold. This important notion has also recently merged from the intensive studies around the homotopy principle in Complex Analysis. This homotopy principle, which goes back to the 1930s, has had an enormous impact on the development of the area of Several Complex Variables and the number of its applications is constantly growing. In this overview chapter we present three classes of properties: (1) density property, (2) flexibility, and (3) Oka–Forstnerič. For each class we give the relevant definitions, its most significant features and explain the known implications between all these properties. Many difficult mathematical problems could be solved by applying the developed theory, we indicate some of the most spectacular ones.