Pharmacological Investigation of Protein Kinase C- and cGMP-Dependent Ion Channels in Cultured Olfactory Receptor Neurons of the Hawkmoth Manduca sexta

In the hawkmoth Manduca sexta, pheromone stimuli of different strength and duration rise the intracellular Ca2+ concentration in olfactory receptor neurons (ORNs). While second-long pheromone stimuli activate protein kinase C (PKC), which apparently underlies processes of short-term adaptation, minute-long pheromone stimuli elevate cyclic guanosine monophosphate (cGMP) concentrations, which correlates with time courses of long-term adaptation. To identify ion channels involved in the sliding adjustment of olfactory sensitivity, inside-out patch clamp recordings on cultured ORNs of M. sexta were performed to characterize Ca2+-, PKC-, and cGMP-dependent ion channels. Stepping to positive holding potentials in high intracellular Ca2+ elicits different Ca2+-dependent ion channels, namely small-conductance channels (2–20 ps), medium-conductance channels (20–100 ps), and large-conductance channels (>100 ps). Ion channels of 40, 60, and 70 ps opened after PKC activation, whereas 10- and >100-ps channels were observed less frequently. Application of 8-bromo cyclic guanosine monophosphate opened 55- and 70-ps channels and increased the open probability of >100-ps channels, whereas even in the presence of phorbol ester 40-ps channels were inhibited. Thus, cGMP elevations activate a different set of ion channels as compared with PKC and suppress at least one PKC-dependent ion channel

Computational Model of the Insect Pheromone Transduction Cascade

A biophysical model of receptor potential generation in the male moth olfactory receptor neuron is presented. It takes into account all pre-effector processes—the translocation of pheromone molecules from air to sensillum lymph, their deactivation and interaction with the receptors, and the G-protein and effector enzyme activation—and focuses on the main post-effector processes. These processes involve the production and degradation of second messengers (IP3 and DAG), the opening and closing of a series of ionic channels (IP3-gated Ca2+ channel, DAG-gated cationic channel, Ca2+-gated Cl− channel, and Ca2+- and voltage-gated K+ channel), and Ca2+ extrusion mechanisms. The whole network is regulated by modulators (protein kinase C and Ca2+-calmodulin) that exert feedback inhibition on the effector and channels. The evolution in time of these linked chemical species and currents and the resulting membrane potentials in response to single pulse stimulation of various intensities were simulated. The unknown parameter values were fitted by comparison to the amplitude and temporal characteristics (rising and falling times) of the experimentally measured receptor potential at various pheromone doses. The model obtained captures the main features of the dose–response curves: the wide dynamic range of six decades with the same amplitudes as the experimental data, the short rising time, and the long falling time. It also reproduces the second messenger kinetics. It suggests that the two main types of depolarizing ionic channels play different roles at low and high pheromone concentrations; the DAG-gated cationic channel plays the major role for depolarization at low concentrations, and the Ca2+-gated Cl− channel plays the major role for depolarization at middle and high concentrations. Several testable predictions are proposed, and future developments are discussed

Spiking Patterns and Their Functional Implications in the Antennal Lobe of the Tobacco Hornworm Manduca sexta

Bursting as well as tonic firing patterns have been described in various sensory systems. In the olfactory system, spontaneous bursts have been observed in neurons distributed across several synaptic levels, from the periphery, to the olfactory bulb (OB) and to the olfactory cortex. Several in vitro studies indicate that spontaneous firing patterns may be viewed as “fingerprints” of different types of neurons that exhibit distinct functions in the OB. It is still not known, however, if and how neuronal burstiness is correlated with the coding of natural olfactory stimuli. We thus conducted an in vivo study to probe this question in the OB equivalent structure of insects, the antennal lobe (AL) of the tobacco hornworm Manduca sexta. We found that in the moth's AL, both projection (output) neurons (PNs) and local interneurons (LNs) are spontaneously active, but PNs tend to produce spike bursts while LNs fire more regularly. In addition, we found that the burstiness of PNs is correlated with the strength of their responses to odor stimulation – the more bursting the stronger their responses to odors. Moreover, the burstiness of PNs was also positively correlated with the spontaneous firing rate of these neurons, and pharmacological reduction of bursting resulted in a decrease of the neurons' responsiveness. These results suggest that neuronal burstiness reflects a physiological state of these neurons that is directly linked to their response characteristics

Institutional models for the back end of the nuclear fuel cycle

As recent developments in the international energy situation have shown, the necessity of utilizing all available sources of energy all over the world has become inevitable. This also necessitates increased application of nuclear energy in the industrialized countries and similarly to an increasing extent in the developing countries. However, the many and varied problems of ecology, economy and public acceptance associated with the peaceful uses of nuclear energy require intensive support and close cooperation in the transfer ofnuclear technology from industrialized to developing countries. In addition to cooperation in the R + D sector, the major priority in nuclear transfer between the developing countries and the industrialized countries was to be found in the past in supplying enriched fuel and reactors. The problern of the management of spent fuel from nuclear power stations and its practical solution will in future also increasingly arise in the developing countries with the growing amounts of spent fuel elements. It therefore appears meaningful to include the issue of managing the back end of the fuel cycle in negotiating the boundary conditions of a nuclear transfer from the supplier states to the recipient states, possibly directly connected e. g. with the expert of nuclear power stations. [...

Institutionelle Modelle für den Bereich der nuklearen Entsorgung

Wie die jüngste Entwicklung der internationalen Energiesituation gezeigt hat, wird die Notwendigkeit, weltweit alle verfügbaren Energiequellen zu nutzen, unumgänglich. Damit wird auch ein verstärkter Einsatz der Kernenergie in den Industrieländern und in wachsendem Maße ebenfalls in den Entwicklungsländern erforderlich. Allerdings benötigen hier die vielfältigen Probleme der Ökologie, der Ökonomie und der öffentlichen Akzeptanz, die mit der Nutzung der friedlichen Kernenergie verbunden sind, eine intensive Hilfestellung und enge Kooperation beim nuklearen Technologietransfer von Industrieländern in Entwicklungsländer. Neben Kooperationen im F + E-Bereich lag das Schwergewicht des Nukleartransfers zwischen Entwicklungsländern und Industrieländern in der Vergangenheit in der Lieferung von angereichertem Brennstoff sowie von Reaktoren. Die Frage der Entsorgung von Kernkraftwerken und deren praktische Lösung wird sich zukünftig in verstärktem Maße mit wachsenden Mengen an abgebrannten Brennelementenauch in den Entwicklungsländern stellen. Deshalb erscheint es sinnvoll, daß die Entsorgungsfrage in die Verhandlungen der Rahmenbedingungen beim Nukleartransfer von Lieferländern in Empfängerländer mit einbezogen und unter Umständen direkt z.B. mit dem Export von Kernkraftwerken verknüpft wird. Ein wesentlicher Gesichtspunkt, der in der Vergangenheit den institutionellenRahmen und die vertragliche Struktur der internationalen Kooperation beim Nuklearhandel bestimmt hat, war der Aspekt der Non-Proliferation. Mit dem Atomwaffensperrvertrag im Jahre 1968 sollte auf der einen Seite ein Festsschreiben des Status Quo im Kernwaffenbereich erreicht und auf der anderen Seite eine möglichst ungehinderte friedliche Nutzung der Kernenergie ermöglichtwerden. Bemühungen von verschiedenen Staaten, sich über den sogenannten friedlichen Sprengkörper faktisch in den Besitz von Kernwaffen zu setzen, führte zu einer Verschärfung der vertraglichen Rahmenbedingungen im internationalen Nuklearbereich und gipfelte insbesondere in den Vereinigten Staaten sogar in der Forderung, auf sensitive Aktivitäten des nuklearen Brennstoffkreislaufes,wie die der Anreicherung oder der Wiederaufarbeitung, völlig zu verzichten. [...