Properties of the ATP-sensitive K+ current activated by levcromakalim in isolated pulmonary arterial myocytes

Tension and patch clamp recording techniques were used to investigate the relaxation of rabbit pulmonary artery and the properties of the K⁺ current activated by levcromakalim in isolated myocytes. Under whole-cell voltage clamp, holding at –60 mV in symmetrical 139 mm K⁺, levcromakalim (10 m) induced a noisy inward current of –116 ± 19 pA (n = 13) which developed over 1 to 2 min. This current could be blocked by either glibenclamide (10 m) or phencyclidine (5–50 M) and was unaffected when extracellular Ca²⁺ was removed. Both these drugs inhibited the levcromakalim-induced relaxation of muscle strips precontracted with 20 mm [K⁺] _o . Application of voltage ramps in symmetrical 139 mm K⁺ confirmed that the levcromakalim-induced current was carried by K⁺ ions and was weakly voltage dependent over the potential range from –100 to +40 mV.The unitary current amplitude and density of the channels underlying the levcromakalim-activated whole-cell K⁺ current was estimated from the noise in the current record. We estimate that levcromakalim caused activation of around 300 channels per cell, with a single channel current of 1.1 pA, corresponding to a slope conductance of about 19 pS. Furthermore, cells dialyzed with an ATP-free pipette solution developed a large noisy inward current at –60 mV, which could subsequently be blocked by flash photolysis of caged ATP. Analysis of the noise associated with this current indicated that the single channel amplitude underlying the ATP-blocked current was 1.4 pA, a value similar to that estimated for the levcromakalim-induced current. We conclude that the conductance of this ATP-sensitive channel is likely to be small under physiological conditions and that it is present at low density.We thank SmithKline & Beecham for the gift of levcromakalim, ICI Pharmaceuticals for the gift of charybdotoxin and Prof. D. Colquhoun for the noise analysis programs. We also thank Mr. R. Davey for technical assistance with tension experiments. This work was supported by the British Heart Foundation and the Wellcome Trust. L.H.C. is a Wellcome Research Fellow and P.L. is an intermediate fellow of the BHF.     

The dynamics of population models with distributed maturation periods

An integro-differential equation for the dynamics of a subpopulation of adults in a closed system where only the adults compete and where there is a distribution of maturation periods is described. We show how the careful choice of a general weighting function based on the gamma distribution with a shift in origin enables us to characterize adequately some observed maturation-period distributions, and also makes local stability and numerical analyses straightforward. Using these results we examine the progression in the behavior of the distributed-delay model as the distribution is narrowed toward the limit of a discrete delay. We conclude that while local stability properties approach those of the limiting equation very rapidly, the persistent fluctuation behavior converges more slowly, with the dominant period and maximum amplitude being least affected by the details of the distribution, and the fine structure of solutions being most sensitive. Finally, we examine the consequences for population modeling, and using several examples of insect populations, conclude that although quite often a full maturation-period distribution should be incorporated in a given model, in many cases a discrete-delay approximation will suffice.     

Age- and density-dependent population dynamics in static and variable environments

We consider a general model of a single-species population with age- and density-dependent per capita birth and death rates. In a static environment we show that if the per capita death rate is independent of age, then the local stability of any stationary state is guaranteed by the requirement that, in the region of the steady state, the density dependence of the birth rate should be negative and that of the death rate positive. In a variable environment we show that, provided the system is locally stable, small environmental fluctuations will give rise to small age structure and population fluctuations which are related to the driving environmental fluctuations by a simple “transfer function.” We illustrate our general theory by examining a model with a per capita death rate which is age and density independent and a per capita birth rate which is zero up to some threshold age a₀, adopts a finite density-dependent value up to a maximum age a_o + α, and is zero thereafter. We conclude from this model that resonance due specifically to single-species age-structure effects will only be of practical importance in populations whose members have a life cycle consisting of a long immature phase followed by a short burst of intense reproductive effort (α a_o).     

Effect of neurotensin on pancreatic function in man

The effect of neurotensin on submaximally-stimulated hepatobiliary and pancreatic secretion was studied in 6 healthy subjects. An intravenous infusion of neurotensin 1.4 ± 0.3 pmol/kg/min, designed to reproduce plasma neurotensin immunoreactivity levels within the physiological range, produced a significant increase in pancreatic bicarbonate output. Plasma concentrations of pancreatic polypeptide rose by 83 ± 16 pmol/l and were associated with a small reduction in trypsin, but no significant change in bilirubin outputs.     

Modelling Coral Reef Futures to Inform Management: Can Reducing Local-Scale Stressors Conserve Reefs under Climate Change?

Climate change has emerged as a principal threat to coral reefs, and is expected to exacerbate coral reef degradation caused by more localised stressors. Management of local stressors is widely advocated to bolster coral reef resilience, but the extent to which management of local stressors might affect future trajectories of reef state remains unclear. This is in part because of limited understanding of the cumulative impact of multiple stressors. Models are ideal tools to aid understanding of future reef state under alternative management and climatic scenarios, but to date few have been sufficiently developed to be useful as decision support tools for local management of coral reefs subject to multiple stressors. We used a simulation model of coral reefs to investigate the extent to which the management of local stressors (namely poor water quality and fishing) might influence future reef state under varying climatic scenarios relating to coral bleaching. We parameterised the model for Bolinao, the Philippines, and explored how simulation modelling can be used to provide decision support for local management. We found that management of water quality, and to a lesser extent fishing, can have a significant impact on future reef state, including coral recovery following bleaching-induced mortality. The stressors we examined interacted antagonistically to affect reef state, highlighting the importance of considering the combined impact of multiple stressors rather than considering them individually. Further, by providing explicit guidance for management of Bolinao''s reef system, such as which course of management action will most likely to be effective over what time scales and at which sites, we demonstrated the utility of simulation models for supporting management. Aside from providing explicit guidance for management of Bolinao''s reef system, our study offers insights which could inform reef management more broadly, as well as general understanding of reef systems.     

Effect of Metalaxyl on the incidence and severity of Pearl millet downy mildew disease in Northern Nigeria

Pearl millet downy mildew (DM) incidence, severity and yield losses of two pearl millet varieties (local and improved) due to the disease were determined in the field. Significant differences in the disease incidence and severity were recorded in the plots sown with metalaxyl-treated seeds and those sown with non-treated seeds, indicating the efficacy of the fungicide on the fungus. Yield losses due to non-treatment of seeds with metalaxyl was 40.88 and 45.39% in a local variety and 43.00 and 18.60% in an improved variety in the 2000 and 2001 cropping seasons respectively. Significant differences between plots sown with metalaxyl-treated and those sown with non-treated seeds were obtained for other yield components such as 1000-grains weight, panicle length and weight.