Pspice model of electrically stimulated isolated brain microtubules is consistent with electrochemical transistor that supports self-sustained oscillations

SMOLER M; PEREZ PL; VILLA ETCHEGOYEN C; CANTERO MR; CANTIELLO HF

Los Ángeles

Congreso; 60th annual Meeting of the Biophysical Society; 2016

Microtubules (MTs) are unique components of the cytoskeleton formed by hollow cylindrical structures of  tubulin dimeric units. MTs are implicated in higher neuronal functions, including memory and the emergence of ??consciousness??. Previous studies from our laboratory (Priel et al, Biophys J, 2006 and 2008) demonstrated that MTs behaves as biomolecular transistors capable of amplifying electrical signals. Herein we implemented an RLC equivalent circuit containing negative resistance and capacitance in the PSPICE platform that supports persistent oscillating currents. The electrochemical reaction is represented by an inductor in the equivalent circuit. The simulation results show that an electrochemical device can be operated as normal transistors or oscillators under different voltage bias. This model predicts that analog circuit functions can be realized with ?inductor-like? electrochemical devices. The simulated results with the model supporting self-supporting current oscillations in the electrochemical device were in good agreement with experimental results obtained under voltage-clamping conditions during short voltage ramp protocols in symmetrical KCl (140 mM), suggesting a functional role of the nanopores in the MT wall. The model supported nonlinear responses with clear negative resistance region. The model is mechanistically consistent with an electrochemical transistor that supports both amplification and self-sustained electrical oscillations. The capacitive current generated by the gate would trigger a nanopore conductance electrodiffusional circuit. Based on the fact that the MT wall could be envisioned as a structural sandwich of negative charges on either side facing adsorbed ions (space charge) from the bulk solution, several transmural capacitors in series would be coupled that have to be charged properly to allow ions through. The model supports that MTs behave as highly synchronized electrical oscillators that could play yet unknown role(s) in biological signaling events, including the transport of electrical information in neurons and MT-driven organelles such as axons, cilia and flagella, as well as the control of cell division.