Electrical Oscillations of Brain Microtubular Structures Horacio F. Cantiello , Cantero Maria Del Rocio; Perez Paula Luciana; Scarinci Maria Noelia; Gutierrez Brenda Celeste (Instituto Multidisciplinario de Salud - Tecnologia y Desarrollo, Instituto Multidisciplinario de Salud, Tecnologia y Desarrollo IMSaTeD (UNSE-CON, Santiago del Estero, Villa El Zanjon Argentina) PL13
It is accepted that the cell's cytoskeleton is an essential structure that conveys specific morphology and phenotypical properties to the various cell types. Not as clearly understood is the role the cytoskeleton plays in the generation and transmission of intracellular electrical signals. Microtubules (MTs), in particular, are unique in that these structures play important roles in cell function, including acting as railways for motor proteins, vesicles and organelles, and separating chromosomes during cell division. MTs are hollow tubes made from alpha-beta-tubulin heterodimers stacked head to tail into protofilaments, which assemble into curled surfaces to form cylindrical structures of different stability within the cytoplasm. Interestingly, several MT arrangements, including macrotubes of larger diameters, bundles, rings, and two-dimensional sheets are also observed in the cell's environment. Stable sheets of protofilaments show distinct structural lattices dependent on the lateral interactions between adjacent alpha-beta-tubulin subunits. Thus, MTs form diverse intracellular superstructures of variable complexity and defined role(s) in cell function. The mitotic spindle, for example, is a large dynamic array of MTs that segregates chromosomes during cell division. The axoneme that structures sensory and motile cilia and flagella is commonly formed by nine doublets of MTs, and triplets of MTs are also observed in centrioles and basal bodies. MTs are also highly charged polyelectrolytes, capable of amplifying electrical signals. The actual physiological nature of these electrodynamic capabilities has only recently begun to unravel by electrophysiological studies. Herein we summarize our most recent advances on our understanding of the electrical properties of different MT structures. We have applied different electrophysiological techniques, including patch clamping and lipid bilayer reconstitution to brain MT structures, to characterize their electrical properties. We improved on the method for patching MTs, obtaining conditions to reach gigaseal-resistance patches of MT sheets that disclosed detailed electrical properties of the preparations tested. We observed a rather remarkable electrical oscillatory behavior of these MT structures that generated cation-selective oscillatory electrical currents whose magnitude and polarity depended on both the electrochemical gradients and chemical composition. The electrical oscillations were spontaneous and progressed through various regimes including complex behaviors, being prominent a fundamental frequency at 39Hz. Under intracellular physiological conditions (140 mM K+), oscillations represented, in average, a 400% change in conductance. Current injection also induced voltage oscillations that showed excitability properties similar to that of action potentials. Also under intracellular-like conditions, similar findings were observed in bundles of brain MTs and other preparations, including membrane-permeabilized neurites of cultured mouse hippocampal neurons. The encompassed evidence indicates that electrical oscillations are an intrinsic property of brain MTs, which may have important implications in the control of various neuronal functions, including the gating and regulation of excitable ion channels and electrical activity to aid and extend to higher brain functions.