Bundles of Brain Microtubules Generate Electrical Oscillations

Abstract

Microtubules (MTs) are long cylindrical structures of the cytoskeleton that control cell division, intracellular transport, and the shape of cells. MTs also form bundles, which are particularly prominent in neurons, where they help define axons and dendrites. MTs are bio-electrochemical transistors that form nonlinear electrical transmission lines. However, the electrical properties of most MT structures remain largely unknown. Here we show that bundles of brain MTs spontaneously generate electrical oscillations and bursts of electrical activity similar to action potentials. Under intracellular-like conditions, voltage-clamped MT bundles displayed electrical oscillations with a prominent fundamental frequency at 39 Hz that progressed through various periodic regimes. The electrical oscillations represented, in average, a 258% change in the ionic conductance of the MT structures. Interestingly, voltage-clamped membrane-permeabilized neurites of cultured mouse hippocampal neurons were also capable of both, generating electrical oscillations, and conducting the electrical signals along the length of the structure. Our findings indicate that electrical oscillations are an intrinsic property of brain MT bundles, which may have important implications in the control of various neuronal functions, including the gating and regulation of cytoskeleton-regulated excitable ion channels and electrical activity that may aid and extend to higher brain functions such as memory and consciousness.

Actin filaments modulate electrical activity of brain microtubule protein two‐dimensional sheets

“…In conclusion, the present study provides experimental evidence for a functional link between the electrical properties of tubulin structures and actin filaments. The data are consistent with an electrostatic interaction between actin filaments and the electrical oscillators present at the MT surface (Cantero et al, ). Also consistent with previous findings, it could be postulated that localized changes in electrostatic potentials arising from interactions between these highly charged polymers and oscillatory changes in the asymmetric ionic distributions between the intra‐ and extra‐MT environments, provide a novel mechanism for intracellular signals (Zhao & Zhan, ).…”

“…Other protofilaments conformations such as the assembly of curled protofilaments are also evidenced (Desai & Mitchison, ). In fact, the flat tubulin structure studied in the present and other recent studies (Cantero et al, ; Cantero et al, ; Cantero, ) are often seen in biological preparations. Erickson () first reported tubulin sheets as intermediates during MT assembly, proposing that tubulins first form a 2D open sheet, which in turn closes into tubes.…”

“…We previously reported that this type of tubulin structure allows electrical configurations of the patch‐clamp technique that render high resistance seals and more reliable electrical information whereupon we were able to detect rather robust electrical oscillations (Cantero et al, ). The fact that similar electrical oscillations were also observed in brain MT bundles (Cantero et al, ), and membrane stripped neurons, supports the potential relevance of this phenomenon, despite the fact that no electrical oscillations, but instead electrical amplification was originally observed in taxol‐attached isolated MTs (Priel et al, ; Priel et al, ; Priel & Tuszynski, ; Priel et al, ). The molecular nature of the oscillations is presently a matter of current study.…”

“…The molecular nature of the oscillations is presently a matter of current study. However, the electrical behavior of tubulin sheets is mechanistically consistent with the behavior of an organic electrochemical transistor that supports both amplification and self‐sustained current‐ (and voltage‐) oscillations (Cantero et al, ; Cantero et al, ). In this model of the MT oscillations, a gate region of the electrochemical transistor would drive the synchronous open‐close cycles of ion‐permeable nanopores that elicit the electrodiffusional circuit.…”

“…In fact, the extremely large uncompensated charge (Zhang & Cantiello, ), and electrostatic interactions between MTs may play an important role in their macromolecular assembling and function (Needleman et al, ). Recently, we demonstrated that different tubulin structures including mammalian 2D‐MT sheets and MT bundles generate strong electrical oscillations (Cantero, Perez, Smoler, Villa Etchegoyen, & Cantiello, ; Cantero, Villa Etchegoyen, Perez, Scarinci, & Cantiello, ) that may help explain the MT's ability to act as a nonlinear transmission line capable of signal amplification (Priel et al, ; Priel et al, ; Priel & Tuszynski, ; Priel, Ramos, Tuszynski, & Cantiello, ; Sekulić, Satarić, Tuszynski, & Satarić, ; Henry, Durai, Net, Balraj, & Priya, ).…”