A single beta subunit M2 domain residue controls the picrotoxin sensitivity of alpha beta heteromeric glycine receptor chloride channels

This study investigated the residues responsible for the reduced picrotoxin sensitivity of the alpha beta heteromeric glycine receptor relative to the alpha homomeric receptor. By analogy with structurally related receptors, the beta subunit M2 domain residues P278 and F282 were considered the most likely candidates for mediating this effect. These residues align with G254 and T258 of the alpha subunit. The T258A, T258C and T258F mutations dramatically reduced the picrotoxin sensitivity of the alpha homomeric receptor. Furthermore, the converse F282T mutation in the beta subunit increased the picrotoxin sensitivity of the alpha beta heteromeric receptor. The P278G mutation in the beta subunit did not affect the picrotoxin sensitivity of the alpha beta heteromer. Thus, a ring of five threonines at the M2 domain depth corresponding to alpha subunit T258 is specifically required for picrotoxin sensitivity. Mutations to alpha subunit T258 also profoundly influenced the apparent glycine affinity. A substituted cysteine accessibility analysis revealed that the T258C sidechain increases its pore exposure in the channel open state. This provides further evidence for an allosteric mechanism of picrotoxin inhibition, but renders it unlikely that picrotoxin las an allosterically acting 'competitive' antagonist) binds to this residue.

Habitat complexity, spatial interference, and "minimum risk distribution": a framework for population stability

In the past century, the debate over whether or not density-dependent factors regulate populations has generally focused on changes in mean population density, ignoring the spatial variance around the mean as unimportant noise. In an attempt to provide a different framework for understanding population dynamics based on individual fitness, this paper discusses the crucial role of spatial variability itself on the stability of insect populations. The advantages of this method are the following: (1) it is founded on evolutionary principles rather than post hoc assumptions; (2) it erects hypotheses that can be tested; and (3) it links disparate ecological schools, including spatial dynamics, behavioral ecology, preference-performance, and plant apparency into an overall framework. At the core of this framework, habitat complexity governs insect spatial variance. which in turn determines population stability. First, the minimum risk distribution (MRD) is defined as the spatial distribution of individuals that results in the minimum number of premature deaths in a population given the distribution of mortality risk in the habitat (and, therefore, leading to maximized population growth). The greater the divergence of actual spatial patterns of individuals from the MRD, the greater the reduction of population growth and size from high, unstable levels. Then, based on extensive data from 29 populations of the processionary caterpillar, Ochrogaster lunifer, four steps are used to test the effect of habitat interference on population growth rates. (1) The costs (increasing the risk of scramble competition) and benefits (decreasing the risk of inverse density-dependent predation) of egg and larval aggregation are quantified. (2) These costs and benefits, along with the distribution of resources, are used to construct the MRD for each habitat. (3) The MRD is used as a benchmark against which the actual spatial pattern of individuals is compared. The degree of divergence of the actual spatial pattern from the MRD is quantified for each of the 29 habitats. (4) Finally, indices of habitat complexity are used to provide highly accurate predictions of spatial divergence from the MRD, showing that habitat interference reduces population growth rates from high, unstable levels. The reason for the divergence appears to be that high levels of background vegetation (vegetation other than host plants) interfere with female host-searching behavior. This leads to a spatial distribution of egg batches with high mortality risk, and therefore lower population growth. Knowledge of the MRD in other species should be a highly effective means of predicting trends in population dynamics. Species with high divergence between their actual spatial distribution and their MRD may display relatively stable dynamics at low population levels. In contrast, species with low divergence should experience high levels of intragenerational population growth leading to frequent habitat-wide outbreaks and unstable dynamics in the long term. Six hypotheses, erected under the framework of spatial interference, are discussed, and future tests are suggested.