Microtubule Electrical Oscillations and Hippocampal Function

Abstract

Microtubules (MTs) are long cylindrical structures of the cytoskeleton that control cell division, vesicular transport, and the shape of cells. MTs are highly charged and behave as nonlinear electrical transmission lines. However, comparatively little is known about the role(s) these nonlinear electrical properties of MTs play in cell function. MTs form bundles, which are particularly prominent in neurons, where they help developmentally define axons and dendrites. The present review summarizes recent work from our laboratory, which demonstrated that 1) bundles of rat brain MTs spontaneously generate electrical oscillations and bursts of electrical activity similar to action potentials; 2) actin filaments control electrostatically the oscillatory response of brain MTs; and 3) neurites of cultured mouse hippocampal neurons generate and propagate electrical oscillations thus, providing a cellular correlate to the isolated MT oscillations. Electrical oscillations are an intrinsic property of brain MT bundles, which may have important implications in the control of various neuronal functions, including a contribution to the intrinsic oscillatory modes of neurons, and thus to higher brain functions, including the formation of memory and the onset of consciousness. Electrical Oscillations of Bundles of Brain Microtubules MTs are unique components of the cytoskeleton that form a wide variety of intracellular superstructures 1. Highly polarized cells such as neurons present two distinct cellular domains, namely the axon and multiple shorter dendrites that either transmit or receive electrical signals, respectively. In both axons and dendrites, MTs form dense parallel arrays known as bundles, which are required for neuronal growth and maintenance of neurites 2. MTs are formed of highly charged α, β tubulin heterodimeric units that behave as biological transistors supporting, amplifying and axially propagating electrical signals 3. Within the cytoplasm MT-generated variable currents may contribute to the presence and modulation of large intracellular electric fields, which in turn, will help control cell function. To determine the electrical activity of bundles of rat brain MTs, we recently used the loose patch-clamp configuration technique 4 on MT bundles isolated from rat brain. These MT structures displayed spontaneous electrical activity consistent with self-sustained oscillations that responded directly to the magnitude of the electrical stimulus (Figure 1). Most frequently, the initial response consisted of strong bursts of oscillations that varied both in amplitude and frequency in the absence of any change in driving force. Interestingly, mean currents were often linear respect to voltage, although spontaneous changes in amplitude of the cyclic regimes were observed as well. Although similar, the oscillatory response of the bundles was richer than that reported for brain MT sheets 5 and more coherent than that observed in isolated MTs 6. Thus, the geometry of the MT assembly