Biomedical subjects

F Elinder

Publications and source records attributed to F Elinder.

23 records · Page 2Linked to original sources

PubMed1991

Mechanisms of the tetrahydroaminoacridine effect on action potential and ion currents in myelinated axons.

9-Amino-1,2,3,4-tetrahydroacridine (THA) in the range of 10-300 microM was shown to prolong the action potential in myelinated nerve fibres of Xenopus laevis. Voltage-clamp experiments showed that THA, besides reducing the Na+ and the K+ current, modified the Na+ current inactivation and the K+ current activation. The effects were frequency dependent. Quantitative models were developed and used in computer simulations of the THA effect on the action potential. The computations showed that the observed effects on the ion currents were sufficient to explain the observed prolongation of the action potential. The models further suggest that THA binds to Na+ channels in an open state and from the axoplasmic side while it binds to K+ channels in a closed state. The findings suggest an explanation to some aspects of the clinical effects of THA on Alzheimer patients.

Action Potentials↗

PubMed1991

Properties of the leakage current pathway: effects of the gadolinium ion on myelinated axons.

Voltage-clamp experiments on myelinated axons revealed that the trivalent gadoliniumion ion blocked the leakage current in a dose-dependent manner. The block showed 1:2 stoichiometry, and 50% reduction at 700 microM. Na+ and K+ currents were blocked at ten times lower concentration and showed 1:1 stoichiometry. Comparisons with biochemical studies suggest that the leakage current directly depends on a phospholipid pathway in contrast to the protein-channel dependent Na+ and K+ currents. The results may be explained by a leakage current pathway located at the interface between channel proteins and the lipid phase.

Animals↗

PubMed1989

Effects of THA on ionic currents in myelinated axons of Xenopus laevis.

In voltage-clamp experiments with the myelinated nerve fibre of Xenopus laevis, 9-amino-1,2,3,4-tetrahydroacridine (THA) decreased both Na+ and K+ currents and shifted the steady state inactivation potential curve in a negative direction. The effects may be described as (a) a decrease of the permeability constant PNa, (b) a modified potential dependence of the inactivating system and (c) a decrease of PK. The Na+ system was affected more than the K+ system.

Aminoacridines↗

PubMedDate not supplied

Non-stationary fluctuation analysis of the Na current in myelinated nerve fibers of Xenopus laevis: experiments and stochastic simulations.

Na current fluctuations under voltage-clamp conditions during pulse steps in the potential range from -65 to -30 mV were measured in myelinated nerve fibers of Xenopus laevis. The covariance functions for four consecutive 1 ms intervals were calculated. The time courses of the covariance functions were well fitted with monoexponential functions with time constants between 0.5 and 3 ms, larger at the end of the pulse and larger at more positive potentials. To analyze the underlying channel kinetics we simulated current fluctuations at a step to -35 mV of eight published Na channel models and calculated corresponding covariance functions. None of the models did explain the experimental fluctuation results. We therefore developed a new Na channel model that satisfactorily described the results. Features that distinguished this model from the other tested ones were a slower deactivation rate, and an inactivation transition directly from a closed state.

Animals↗

PubMedDate not supplied

Na channel kinetics: developing models from non-stationary current fluctuations by analytic methods.

In a previous study, we analyzed Na current fluctuations in myelinated axons from Xenopus laevis under voltage clamp conditions. The statistical properties were analyzed in terms of covariance functions for consecutive time intervals of varying duration during the pulse step. The underlying channel kinetics was analyzed by performing stochastic simulations of published Na channel models and calculating corresponding covariance functions. None of the models explained the fluctuation results. We therefore developed a novel minimal Na channel model that satisfactorily described the results. In the present paper, we extend the analysis and specify the possible models explaining the experimental data by using analytical methods. We derive general relations between the experimental data, including the covariance functions, and the rate constants of specific one-open-state models. A general feature of these models is that they comprise an inactivation step from the first closed state and a relatively low backward rate from the open state. This is in accordance the minimal model inferred from numerical stochastic calculations in the previous study.

Animals↗