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No description available.

Ion channel models are related to non-equilibrium statistical physics, fluid mechanics and electromagnetism. Some classes of ordinary differential equations that model ion channels can be seen as a limit of finite state-space continuous-time Markov chains. The purpose of this thesis is to qualitatively investigate the numerical results of systems of equations that incorporate ion channels modeled by such Markov chains and an electrical circuit model of a single neuron with isopotential extracellular space. This may be useful for making more detailed micro-physical simulations of neurons. A subset of the Rallpack benchmarks is conducted in order to evaluate the accuracy of the electrical circuit model of the transmembrane voltage propagation. In order to test the tau-leap method employed to simulate the Markov-chain based ion channel models a cylindrical geometry is implemented. Convergence properties are presented in terms of mean interspike intervals of the transmembrane voltages for different time- and spatial discretisations. Accuracy of the tau-leap method is presented in relation to the deterministic versions of the ion channel models. The results show that the method used to simulate the transmembrane voltages is accurate and that while the tau-leap method is convergent in the mean interspike interval sense, it is not conclusive how accurate it is compared to the corresponding ordinary differential equations or how efficient it is.

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The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of impaired neuromuscular transmission. It is associated with small cell lung carcinoma (SCLC) in 60% of patients. There is considerable evidence that the defect in LEMS is caused by autoantibodies to voltage-gated calcium channels (VGCCs) on the nerve terminal. Two VGCC subtypes were demonstrated in cultured neuronal cell lines by the technique of K⁺-induced ⁴⁵Ca²⁺ influx: one subtype was inhibited by dihydropyridines (DHPs), the other by ω-conotoxin (ωCgTx). These may correspond to L and N channels previously described for neuronal tissue. The presence of these VGCC subtypes was confirmed by radioligand binding studies using [3 Hj-PN200-11 0 and 125 I-d)ωCgTx respectively. Pooled LEMS IgG inhibited K⁺-induced Ca²⁺ flux by 40% in SKNSH (human neuroblastoma) cells, while control IgG had no effect. The same LEMS pool reduced the density of ¹²⁵I-ωCgTx binding sites in SKNSH and MAR5 (human SCLC) cells by 57% and 43% respectively. These results provide further evidence that LEMS antibodies cause a loss of functional VGCCs. 78 LEMS and 88 control sera were tested for anti-VGCC antibodies by the precipitation of ¹²⁵I-ωCgTx-labelled VGCCs extracted from SKNSH cells. 42% of LEMS sera had significant levels of antibody (30-1466pM) compared to the healthy controls (<31pM). There was a high correlation between these results and those obtained using antigen extracted from MAR5 cells. Raised antibody titres (30-82pM) were also found among SCLC patients (47%) and patients with rheumatoid arthritis or systemic lupus erythematosus (56%). The incidence of positive sera was not significant among patients with other neurological disorders, including myasthenia gravis. Antibody titre did not correlate with disease severity across individuals. However, longitudinal studies in two LEMS patients showed an inverse relation between antibody titre and an electromyographic index of disease severity. Some of the antibodies detected may, therefore, be implicated in the neurological symptoms of LEMS. The assay may be a useful aid for the diagnosis of LEMS in some patients.

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国立情報学研究所で電子化したコンテンツを使用している。

国立情報学研究所で電子化したコンテンツを使用している。

国立情報学研究所で電子化したコンテンツを使用している。