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M Postma

Publications and source records attributed to M Postma.

6 recordsLinked to original sources

The effect of neuronal morphology and membrane-permeant weak acid and base on the dissipation of depolarization-induced pH gradients in snail neurons.

Neuronal depolarization causes larger intracellular pH (pH(i)) shifts in axonal and dendritic regions than in the cell body. In this paper, we present evidence relating the time for collapse of these gradients to neuronal morphology. We have used ratiometric pH(i) measurements using 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) in whole-cell patch-clamped snail neurons to study the collapse of longitudinal pH gradients. Using depolarization to open voltage-gated proton channels, we produced alkaline pH(i) microdomains. In the absence of added mobile buffers, facilitated H(+) diffusion down the length of the axon plays a critical role in determining pH(i) microdomain lifetime, with axons of approximately 100 microm allowing pH differences to be maintained for >60 s. An application of mobile, membrane-permeant pH buffers accelerated the collapse of the alkaline-pH gradients but, even at 30 mM, was unable to abolish them. Modeling of the pH(i) dynamics showed that both the relatively weak effect of the weak acid/base on the peak size of the pH gradient and the accelerated collapse of the pH gradient could be due to the time taken for equilibration of the weak acid and base across the cell. We propose that appropriate weak acid/base mixes may provide a simple method for studying the role of local pH(i) signals without perturbing steady-state pH(i). Furthermore, an extrapolation of our in vitro data to longer and thinner neuronal structures found in the mammalian nervous system suggests that dendritic and axonal pH(i) are likely to be dominated by local pH(i)-regulating mechanisms rather than simply following the soma pH(i).

Acids↗

Neutrinos produced by ultrahigh-energy photons at high redshift.

Some of the proposed explanations for the origin of ultrahigh-energy cosmic rays invoke new sources of energetic photons (e.g., topological defects, relic particles, etc.). At high redshift, when the cosmic microwave background has a higher temperature but the radio background is low, the ultrahigh-energy photons can generate neutrinos through pair production of muons and pions. The resulting diffuse background of 10(17) eV neutrinos can be detected by future experiments.

Journal Article↗

A diffusion-translocation model for gradient sensing by chemotactic cells.

Small chemotactic cells like Dictyostelium and neutrophils transduce shallow spatial chemoattractant gradients into strongly localized intracellular responses. We show that the capacity of a second messenger to establish and maintain localized signals, is mainly determined by its dispersion range, lambda = the square root of D(m)/k(-1), which must be small compared to the cell's length. Therefore, short-living second messengers (high k(-1)) with diffusion coefficients D(m) in the range of 0-5 microm(2) s(-1) are most suitable. Additional to short dispersion ranges, gradient sensing may include positive feedback mechanisms that lead to local activation and global inhibition of second-messenger production. To introduce the essential nonlinear amplification, we have investigated models in which one or more components of the signal transduction cascade translocate from the cytosol to the second messenger in the plasma membrane. A one-component model is able to amplify a 1.5-fold difference of receptor activity over the cell length into a 15-fold difference of second-messenger concentration. Amplification can be improved considerably by introducing an additional activating component that translocates to the membrane. In both models, communication between the front and the back of the cell is mediated by partial depletion of cytosolic components, which leads to both local activation and global inhibition. The results suggest that a biochemically simple and general mechanism may explain various signal localization phenomena not only in chemotactic cells but also those occurring in morphogenesis and cell differentiation.

Animals↗

Does Ca2+ reach millimolar concentrations after single photon absorption in Drosophila photoreceptor microvilli?

The quantum bump, the elementary event of fly phototransduction induced by the absorption of a single photon, is a small, transient current due to the opening of cation-channels permeable to Ca2+. These channels are located in small, tube-like protrusions of the cell membrane, the microvilli. Using a modeling approach, we calculate the changes of free Ca2+ concentration inside the microvilli, taking into account influx and diffusion of Ca2+. Independent of permeability ratios and Ca2+ buffering, we find that the free Ca2+ concentrations rise to millimolar values, as long as we assume that all activated channels are located in a single microvillus. When we assume that as much as 25 microvilli participate in a single bump, the free Ca2+ concentration still reaches values higher than 80 microM. These very high concentrations show that the microvilli of fly photoreceptors are unique structures in which the Ca2+ signaling is even more extreme than in calcium concentration microdomains very close to Ca2+ channels.

Animals↗

HIV-associated dementia: clinical, epidemiological and resource utilization issues.

Among mental disorders associated with HIV infection, dementia is the one most likely to have a major impact on public health, both as a result of the high levels of individual disability, and the greater demand of health care resource utilization. Epidemiologic and economic impact of HIV-associated dementia needs to be estimated, in order to provide policy makers and health managers with the information required for decision making and resource allocation. An increase in HIV encephalopathy prevalence rates may be expected as a consequence of longer survival time in dementia patients and in patients with other AIDS defining disease (longer survival increases the risk of developing HIV encephalopathy). A resource utilization study shows that, in the chronic stage of the disease, in-patient days per person-year are almost double in AIDS subjects with neurological complications as compared with those without neurological complications; no major difference appears when considering out-patients consultations and day-care treatments. In conclusion, a significant rise in resource utilization and in related costs may be anticipated as a consequence of the increasing prevalence of HIV encephalopathy. Further studies seem necessary to compare different approaches in the management of this debilitating disease, in view of a more rational utilization and allocation of resources.

AIDS Dementia Complex↗