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"Phase portrait of cell membrane passive depolarization"

Relatore: Gaetano Aiello- Dipartimento di Fisica & Tecnologie Relative - Palermo

Aula Boltzmann
23 Febbraio 2005 ore 15.30

Abstract When ions leak through the cell membrane the voltage across slowly drifts towards depolarization. Very little is known about the dynamics of this process except that it is very slow. Sustained, prolonged activity, however, would be impossible without the action of the ionic pumps, which ultimately guarantees the correct amplitude of the AP, and the return of the membrane voltage to the resting level. The length of time a neuron could fire with its metabolic pumps blocked (e.g., poisoned by oubain) or lagging behind the rate of firing, has not been determined yet. In the case of paroxistic firing induced by a neurotoxicant this becomes an important issue. In neurons, organotins (especially TMT reduceGABAergic inhibition, enhancing at the same time the release of glutamate. The combined action causes hyperexcitation, and therefore a quite prolonged firing. Even at full power, the pumps might be unable to stand the demands of paroxistic firing induced by a neurotoxicant. As a consequence, the baseline of the spike train is expected to rise to a value no longer compatible with the generation of a typical action potential, or even interfere with the mechanism of generation of the AP itself. Sudden, complete cessation of burst activity has actually been reported in cultured neuronal networks exposed to critical concentrations of TMT [Gramowski]. cute TMT intoxication did not apparently cause permanent cellular damage, and a fully functional recovery was claimed after washing out the medium. Among the possible causes accounting for the shut-off mechanism,a generic “suppression of action potential generation” as suggested. We do favor this hypothesis, hereby providing a plausible shutoff mechanism within the framework of the dynamics of passive depolarization. OUTLINE o Membrane potential rivisited o The cell as a nonlinear dynamical system o Flow in the phase space o Phase Portrait and Stability