Hodgkin-huxley model indicates an inversion in the strength-duration curves for mono and biphasic stimuli

Action potentials are non-linear variations of the transmembrane potential caused by changes in the membrane conductance. In 1952, Hodgkin and Huxley proposed a set of differential equations that describes mathematically the conductance changes observed during the course of an action potential. Currently, this model is still a good tool for understanding the basic mechanisms involved in the initiation and propagation of the action potentials. The objective of this work was to use a simple application of the Hodgkin-Huxley model to define the relation between the stimulation threshold and variations of the stimulatory waveform, in order to promote cell excitation delivering the lowest energy stimulus. We evaluated the strength-duration curves for mono and biphasic stimuli, giving special attention to short stimuli. This Hodgkin-Huxley implementation allowed the explanation of the mechanisms underlining a curious inversion of the strength-duration curves for mono and biphasic stimuli. Namely, for shorter stimuli (<2.2 ms), the stimulation threshold for monophasic stimuli becomes smaller than for biphasic stimuli. That inversion seems to be a result of the time-dependence of the activation variables of Na+ and K+ channels and the inactivation variable of Na+ channels proposed in the Hodgkin-Huxley model. In addition, we used the model to evaluate the energy of asymmetrical biphasic stimuli in order to find a more energy-efficient waveform, which was shown to be a combination of a 7 ms long hyperpolarizing phase with a depolarizing phase of 6 ms.7015762CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES408617/2017-9Sem informação26. Brazilian Congress on Biomedical Engineerin

MAP65/Ase1 promote microtubule flexibility.

International audienceMicrotubules (MTs) are dynamic cytoskeletal elements involved in numerous cellular processes. Although they are highly rigid polymers with a persistence length of 1-8 mm, they may exhibit a curved shape at a scale of few micrometers within cells, depending on their biological functions. However, how MT flexural rigidity in cells is regulated remains poorly understood. Here we ask whether MT-associated proteins (MAPs) could locally control the mechanical properties of MTs. We show that two major cross-linkers of the conserved MAP65/PRC1/Ase1 family drastically decrease MT rigidity. Their MT-binding domain mediates this effect. Remarkably, the softening effect of MAP65 observed on single MTs is maintained when MTs are cross-linked. By reconstituting physical collisions between growing MTs/MT bundles, we further show that the decrease in MT stiffness induced by MAP65 proteins is responsible for the sharp bending deformations observed in cells when they coalign at a steep angle to create bundles. Taken together, these data provide new insights into how MAP65, by modifying MT mechanical properties, may regulate the formation of complex MT arrays