Biomedical subjects

K E Kaissling

Publications and source records attributed to K E Kaissling.

15 recordsLinked to original sources

PubMed2001

Olfactory perireceptor and receptor events in moths: a kinetic model.

A mathematical model of perireceptor and receptor events has been developed for olfactory sensilla on the antennae of the moth Antheraea polyphemus. The model includes the adsorptive uptake of pheromone molecules by the olfactory hair, their transport on and within the hair by diffusion, the formation of a complex of pheromone and the extracellular pheromone-binding protein (PBP), the interaction of the complex pheromone-PBP with the hypothetical receptor molecule on the plasma membrane of the olfactory cell, the deactivation of the pheromone and, finally, its enzymatic degradation. In the model the PBP with its reduced form (with one or two intramolecular disulfide bonds) first acts as a carrier of the odorant. Later, while the pheromone is bound, it changes to an oxidized form (three disulfide bonds) with a scavenger function (carrier-to-scavenger model). This process of pheromone deactivation rather than the enzymatic pheromone degradation is responsible for the fall of the receptor potential after stimulus offset. The model is based on morphometrical, radiometrical, electrophysiological and biochemical data reported by several authors. The study supports the idea that peripheral events rather than intracellular signalling processes govern the kinetics of the receptor potential in the unadapted receptor cell.

Animals↗

PubMed1998

A quantitative model of odor deactivation based on the redox shift of the pheromone-binding protein im moth antennae.

Recent in vitro experiments with homogenates of isolated olfactory hairs of Antheraea polyphemus suggest that the pheromone-binding protein (PBP) is involved not only in pheromone solubilization and transport but also in pheromone deactivation. PBP occurs in a reduced form with one or two disulfide bridges (PBP(red)) and in the oxidized form with three bridges (PBP(ox)). From kinetic experiments it was concluded that the pheromone is first bound to PBP(red). This complex activates the receptor molecules and then turns into the oxidized form which--according to our working hypothesis--is unable to activate further receptor molecules. Apparently, the pheromone bound to the PBP (both forms) is protected from enzymatic degradation into nonexcitatory metabolites. A quantitative kinetic model of pheromone deactivation was developed (in collaboration with J. Thorson, Oxford) in which the receptor molecules are considered to act as enzymes catalyzing the redox shift of the binding protein.

Animals↗

PubMed1998

Flux detectors versus concentration detectors: two types of chemoreceptors.

Dose-response curves relating the external stimulus concentration to receptor occupancy differ in two types of chemoreceptor organs. In 'concentration detectors' the receptor molecules at the receptor cell membrane are directly exposed to the external stimulus concentration; these organs exhibit the well-known hyperbolic dose-response relationship reflecting the association-dissociation of stimulus and receptor molecules. In contrast, 'flux detectors' accumulate the stimulus molecules in a perireceptor compartment. In flux detectors, deactivation of stimulus molecules may be in balance with arrival, as a prerequisite for producing a constant effective stimulus concentration at constant adsorptive flux of stimulus molecules. In a simple model of a flux detector in which receptor molecules themselves catalyze the deactivation, the dose-response relationship is linear. It reflects the rate of stimulus deactivation. If the deactivation is catalyzed by a separate enzyme, the dose-response relationship can be close to hyperbolic, or linear. In all cases, the receptor molecules are maximally occupied if the adsorptive flux equals or exceeds the maximum rate of stimulus deactivation. The time course of the receptor potential recorded from moths' pheromone receptors depends on the odor compound, which suggests that a peripheral process, possibly the stimulus deactivation, is the slowest, rate-limiting process of the transduction cascade. Further evidence comes from experiments with stimuli oversaturating the mechanism responsible for the decline of the receptor potential.

Catalysis↗

PubMed1998

Pheromone deactivation catalyzed by receptor molecules: a quantitative kinetic model.

A quantitative model of pheromone-receptor interaction and pheromone deactivation, the supposed rate-limiting processes underlying the receptor potential kinetics, is worked out for the moth Antheraea polyphemus. In this model, the pheromone interacts with the receptor molecule while bound to the reduced form of the pheromone binding protein. The receptor molecules--besides their receptor function--catalyze the observed shift of the pheromone-binding protein from the reduced to the oxidized form (Ziegelberger, G., Eur. J. Biochem., 232, 706-711, 1995), which deactivates the pheromone bound to pheromone binding protein. With the following parameters, the model fits morphological, radiometric, electrophysiological and biochemical data: a maximum estimate of 1.7 x 10(7) receptor molecules/cell (with 40,000 units/micron 2 of receptor cell membrane), rate constants k1 = 0.2/(s.microM) for the association, k2 = 10/s for the dissociation of the ternary complex of binding protein, pheromone and receptor, and k3 = 10/s for the deactivation via the redox shift. With these parameters, the duration of elementary receptor potentials elicited by single pheromone molecules (approximately 50 ms) reflects the lifetime of the ternary complex, tau = 1/(k2 + k3). The receptor occupancy produced by the model for threshold stimuli fits the sensitivity of the receptor cell to single pheromone molecules.

Animals↗

PubMed1996

Peripheral mechanisms of pheromone reception in moths.

Moths pheromones mostly consist of two or a few chemical components in a species-specific ratio. Each component is perceived by a particular type of receptor cell. Some pheromone components can inhibit the behavioral responses to other pheromone components. A single pheromone molecule is sufficient to elicit a nerve impulse. The dose-response curve of single pheromone receptor neurons increases over many decades of stimulus intensity. Pheromone receptor cells can resolve single stimulus pulses up to a frequency of 10 pulses/s. Electrophysiological and biochemical studies on perireceptor events suggest that the pheromone molecules interact with the receptor cell while bound to a reduced form of the pheromone binding protein. The enzymatic degradation of pheromone found on the antennae is much too slow to account for the decline of the receptor potential after end of stimulation. The postulated rapid deactivation of the odor molecules absorbed might be performed by an oxidation of the pheromone binding protein. Several second messenger systems seem to be involved in the cellular transduction mechanism (IP3, diacylglycerol, cGMP, Ca2+). It is, however, not excluded that pheromone molecules can gate single ion channels directly and thus elicit the elementary receptor potentials, observed at weak stimulus intensities.

Animals↗

PubMed1995

Esterase activity in the olfactory sensilla of the silkmoth Antheraea polyphemus.

We studied in individual males of Antheraea polyphemus the activity of the sensillar esterase, a pheromone-degrading enzyme present in the sensillum lymph surrounding the olfactory receptor cells. In parallel, receptor potentials from single pheromone-sensitive sensilla trichodea were recorded. Our screening revealed a large variability of the enzyme activity in individuals with similar electrophysiological responses. In some moths the sensillar esterase was not detectable, i.e. present with 100-fold less activity. However, such variable esterase activity showed no correlation to the time course of the receptor potential. Thus, enzymatic pheromone degradation does not seem to be involved in the rapid pheromone inactivation at the end of the stimulus, but rather serves as the final pheromone sequestration step.

Animals↗

PubMed1995

The site of action of general anaesthetics in insect olfactory receptor neurons.

The effect of volatile anaesthetics such as N2O, Xe, short-chain alkanes and cyclopropane, at pharmacologically relevant concentrations, on olfactory receptor neurons of insects was tested in electrophysiological recordings. CO2-receptor neurons in moths and flies respond with increased action potential activity, whereas in honeybees the effect is inhibitory. With increasing chain length of the alkanes, the effectiveness increases initially, in adherence to the Meyer-Overton rule; alkanes of a chain length of 5 and above are less effective or evoke suppression of action potentials. In olfactory receptor neurons sensitive to benzoic acid in female moths of Bombyx mori and in pheromone receptor neurons of male moths of Antheraea polyphemus, anaesthetics are ineffective if applied alone; if superimposed on an excitatory olfactory stimulus, an inhibitory effect occurs. Local stimulation of only part of a sensory dendrite reveals that the anaesthetics are effective only if applied at the same location as the excitatory stimulus. This indicates that the anaesthetics reversibly block the reception of pheromone or its effect on the conductance of the receptor cell membrane. The observed interactions are consistent with the hypothesis that the anaesthetics do not interact with the primary transduction process, but rather affect a later stage such as the activation of ion channels.

Action Potentials↗

PubMed1990

Cyclic GMP levels and guanylate cyclase activity in pheromone-sensitive antennae of the silkmoths Antheraea polyphemus and Bombyx mori.

Female sex pheromones applied to freshly isolated, living antennae of male Antheraea polyphemus and Bombyx mori led to an increase of cGMP. A 1:1 mixture of 2 pheromone components of Antheraea polyphemus blown for 10 sec in physiological concentrations over their antennal branches raised cGMP levels about 1.34-fold (+/- 0.08 SEM, n = 23) from a basal level of 3.0 +/- 0.6 (SEM, n = 20) pmol/mg protein. Similarly, bombykol elicited a 1.29-fold (+/- 0.13 SEM, n = 23) cGMP increase in antennae of male Bombyx mori from a basal level of 2.7 +/- 0.5 (SEM, n = 24) pmol/mg protein. No cross-sensitivity was found with respect to pheromones from either species. In antennae of female silkmoths, the cGMP response was missing upon stimulation with their own respective pheromones according to the known lack of pheromone receptor cells in the female. cAMP levels in the male antennae of 14.2 +/- 2.9 (SEM, n = 4) pmol/mg protein in A. polyphemus and 15.0 +/- 3.0 (SEM, n = 5) pmol/mg protein in B. mori were not affected by pheromone stimulation. Within 1-60 sec, the extent of cGMP increase in B. mori was independent of the duration of pheromone exposure. The levels of cGMP in pheromone-stimulated antennae of both species remained elevated for at least 10 min, i.e., much longer than the duration of the receptor potential measured in single-cell recordings. Guanylate cyclase activity was identified in homogenates of male and female antennae from both species. The Km of the guanylate cyclase from male B. mori for the preferential substrate MnGTP was 175 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Adaptation processes in insect olfactory receptors. Mechanisms and behavioral significance.

Adaptation was studied in single olfactory receptor cells of male moths of Bombyx mori and Antheraea polyphemus. Receptor potential and nerve impulse generators have different and very likely, spatially separate adaptation mechanisms possibly located in the outer dendritic segment and the cell soma, respectively. Restricted portions of the receptor cell dendrite can be locally adapted. The impulse generator may exhibit at least two distinct adaptation processes with different kinetics, as deduced from a consideration of the phasic-tonic response and the different adaptation properties of each of these phases. The response characteristics of cells in the same sensillum are different. The "faster" responding cell types resolve odor pulses with frequencies up to 10 per second--a performance that is probably needed for orientation during flight toward a small odor source.

Adaptation, Physiological↗

PubMed1986