Characterization of calcium-dependent potassium channels in antennal receptor neurones of Locusta migratoria

Wegener J, Tareilus E, Breer H. Characterization of calcium-dependent potassium channels in antennal receptor neurones of Locusta migratoria. Journal of Insect Physiology. 1992;38(4):237-248.Antennal receptor neurones from Locusta migratoria were identified by their bipolar morphology and their immunoreactivity with anti-horseradish-peroxidase antibodies. Using patch clamp techniques, an ion channel displaying a high conductance (180 ± 5 pS) and a strong selectivity for potassium ions was detected in somata membranes from these neurones. The channel activity was regulated by intracellular calcium concentrations and by membrane voltage. Intracellular ATP (5 mM) was shown to inhibit channel activity. This channel may be involved in signal transduction of antennal olfactory neurones by controlling their electrical activity

Olfactory signalling in antennal receptor neurones of the locust (Locusta migratoria)

Wegener J, Boekhoff I, Tareilus E, Breer H. Olfactory signalling in antennal receptor neurones of the locust (Locusta migratoria). Journal of Insect Physiology. 1993;39(2):153-163

Structures and functions of calcium channel beta subunits

Calcium channel beta subunits have profound effects on how alpha(1) subunits perform. In this article we summarize our present knowledge of the primary structures of beta subunits as deduced from cDNAs and illustrate their different properties. Upon co-expression with alpha(1) subunits, the effects of beta subunits vary somewhat between L-type and non-L-type channels mostly because the two types of channels have different responses to voltage which are affected by beta subunits, such as lone-lasting prepulse facilitation of alpha(1C) (absent in alpha(1E)) and inhibition by G protein beta gamma dimer of alpha(1E), absent in alpha(1C). One beta subunit, a brain beta 2a splice variant that is palmitoylated, has several effects not seen with any of the others, and these are due to palmitoylation. We also illustrate the finding that functional expression of alpha(1) in oocytes requires a beta subunit even if the final channel shows no evidence for its presence. We propose two structural models for Ca2+ channels to account for "alpha(1) alone" channels seen in cells with limited beta subunit expression. In one model, beta dissociates from the mature alpha(1) after proper folding and membrane insertion. Regulated channels seen upon co-expression of high levels of beta would then have subunit composition alpha(1)beta In the other model, the "chaperoning" beta remains associated with the mature channel and "alpha(1) alone" channels would in fact be alpha(1)beta channels. Upon co-expression of high levels of beta the regulated channels would have composition [alpha(1)beta]beta

An Ordered Water Channel in Staphylococcus aureus

One third of all drugs in clinical use owe their pharmacological activity to the functional inhibition of enzymes, highlighting the importance of enzymatic targets for drug development. Because of the close relationship between inhibition and catalysis, understanding the recognition and turnover of enzymatic substrates is essential for rational drug design. Although the Staphylococcus aureus enoyl-acyl carrier protein reductase (saFabI) involved in bacterial fatty acid biosynthesis constitutes a very promising target for the development of novel, urgently needed anti-staphylococcal agents, the substrate binding mode and catalytic mechanism remained unclear for this enzyme. Using a combined crystallographic, kinetic and computational approach, we have explored the chemical properties of the saFabI binding cavity, obtaining a consistent mechanistic model for substrate binding and turnover. We identified a water-molecule network linking the active site with a water basin inside the homo-tetrameric protein, which seems to be crucial for the closure of the flexible substrate binding loop as well as for an effective hydride and proton transfer during catalysis. Based on our results, we also derive a new model for the FabI-ACP complex that reveals how the ACP-bound acyl-substrate is injected into the FabI binding crevice. These findings support the future development of novel FabI inhibitors that target the FabI-ACP interface leading to the disruption of the interaction between these two proteins